chr14-102929723-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030943.4(AMN):c.829A>G(p.Thr277Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00629 in 1,550,414 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T277T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0046 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0065 ( 43 hom. )

Consequence

AMN
NM_030943.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.92

Publications

3 publications found

Variant links:

Genes affected

AMN (HGNC:14604): (amnion associated transmembrane protein) The protein encoded by this gene is a type I transmembrane protein. It is thought to modulate bone morphogenetic protein (BMP) receptor function by serving as an accessory or coreceptor, and thus facilitates or hinders BMP binding. It is known that the mouse AMN gene is expressed in the extraembryonic visceral endoderm layer during gastrulation, but it is found to be mutated in amnionless mouse. The encoded protein has sequence similarity to short gastrulation (Sog) and procollagen IIA proteins in Drosophila. [provided by RefSeq, Jul 2008]

AMN Gene-Disease associations (from GenCC):

Imerslund-Grasbeck syndrome type 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Imerslund-Grasbeck syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

AMN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005910963).

BP6

Variant 14-102929723-A-G is Benign according to our data. Variant chr14-102929723-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 463391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00457 (695/152030) while in subpopulation SAS AF = 0.0122 (59/4818). AF 95% confidence interval is 0.00975. There are 5 homozygotes in GnomAd4. There are 307 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030943.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMN	NM_030943.4	MANE Select	c.829A>G	p.Thr277Ala	missense	Exon 8 of 12	NP_112205.2	Q9BXJ7-1
	AMN	NM_001425246.1		c.667A>G	p.Thr223Ala	missense	Exon 8 of 12	NP_001412175.1	B3KP64

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMN	ENST00000299155.10	TSL:1 MANE Select	c.829A>G	p.Thr277Ala	missense	Exon 8 of 12	ENSP00000299155.6	Q9BXJ7-1
AMN	ENST00000872999.1		c.772A>G	p.Thr258Ala	missense	Exon 8 of 12	ENSP00000543058.1
AMN	ENST00000559789.1	TSL:3	c.125-442A>G		intron	N/A	ENSP00000452831.1	H0YKJ5

Frequencies

GnomAD3 genomes

AF:

0.00458

AC:

695

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00696

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00496

AC:

766

AN:

154394

AF XY:

0.00527

show subpopulations

Gnomad AFR exome

AF:

0.000860

Gnomad AMR exome

AF:

0.00395

Gnomad ASJ exome

AF:

0.00106

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00615

Gnomad OTH exome

AF:

0.00712

GnomAD4 exome

AF:

0.00648

AC:

9060

AN:

1398384

Hom.:

Cov.:

AF XY:

0.00661

AC XY:

4558

AN XY:

689842

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

31634

American (AMR)

AF:

0.00418

AC:

150

AN:

35880

Ashkenazi Jewish (ASJ)

AF:

0.000596

AC:

AN:

25176

East Asian (EAS)

AF:

0.0000279

AC:

AN:

35832

South Asian (SAS)

AF:

0.00897

AC:

711

AN:

79244

European-Finnish (FIN)

AF:

0.00135

AC:

AN:

48158

Middle Eastern (MID)

AF:

0.00833

AC:

AN:

5040

European-Non Finnish (NFE)

AF:

0.00713

AC:

7692

AN:

1079486

Other (OTH)

AF:

0.00608

AC:

352

AN:

57934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

568

1136

1703

2271

2839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

290

580

870

1160

1450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00457

AC:

695

AN:

152030

Hom.:

Cov.:

AF XY:

0.00413

AC XY:

307

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

41494

American (AMR)

AF:

0.00510

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.000195

AC:

AN:

5116

South Asian (SAS)

AF:

0.0122

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00696

AC:

473

AN:

67914

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00595

Hom.:

Bravo

AF:

0.00473

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000953

AC:

ESP6500EA

AF:

0.00533

AC:

ExAC

AF:

0.00216

AC:

215

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Imerslund-Grasbeck syndrome (1)

Imerslund-Grasbeck syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.24

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.21

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.84

MutationAssessor

Benign

-0.34

PhyloP100

-1.9

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.2

REVEL

Benign

0.17

Sift

Benign

0.64

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.052

MVP

0.51

MPC

0.50

ClinPred

0.0027

GERP RS

-4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.51

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over