Genetic Variant AMN:p.Val7Val (chr14-102922709-C-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_030943.4(AMN):c.21C>A(p.Val7Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000407 in 1,596,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V7V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

AMN
NM_030943.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.409

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 14-102922709-C-A is Benign according to our data. Variant chr14-102922709-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1633325.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.409 with no splicing effect.

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.21C>A	p.Val7Val	synonymous	Exon 1 of 12	NP_112205.2	Q9BXJ7-1
	AMN	NM_001425246.1		c.-161C>A		5_prime_UTR	Exon 1 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.21C>A	p.Val7Val	synonymous	Exon 1 of 12	ENSP00000299155.6	Q9BXJ7-1
AMN	ENST00000872999.1		c.21C>A	p.Val7Val	synonymous	Exon 1 of 12	ENSP00000543058.1
AMN	ENST00000541086.5	TSL:2	n.-213C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000274

AC:

AN:

218760

AF XY:

0.0000421

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000620

Gnomad NFE exome

AF:

0.0000506

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000415

AC:

AN:

1444092

Hom.:

Cov.:

AF XY:

0.0000460

AC XY:

AN XY:

717118

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33370

American (AMR)

AF:

0.00

AC:

AN:

42346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25724

East Asian (EAS)

AF:

0.00

AC:

AN:

39234

South Asian (SAS)

AF:

0.00

AC:

AN:

83344

European-Finnish (FIN)

AF:

0.000103

AC:

AN:

48588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5176

European-Non Finnish (NFE)

AF:

0.0000479

AC:

AN:

1106540

Other (OTH)

AF:

0.0000335

AC:

AN:

59770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000540

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Imerslund-Grasbeck syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.9

(source)

DANN

Benign

0.81

PhyloP100

-0.41

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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