chr14-102929723-A-G

Position:

chr14-102929723-A-G

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

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 links:

AMN (HGNC:):

AMN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMN	NM_030943.4 linkuse as main transcript	c.829A>G	p.Thr277Ala	missense_variant	8/12	ENST00000299155.10	NP_112205.2	Q9BXJ7-1
AMN	XM_011537202.4 linkuse as main transcript	c.667A>G	p.Thr223Ala	missense_variant	8/12			B3KP64
AMN	XM_011537203.4 linkuse as main transcript	c.667A>G	p.Thr223Ala	missense_variant	8/12		XP_011535505.1	B3KP64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AMN	ENST00000299155.10 linkuse as main transcript	c.829A>G	p.Thr277Ala	missense_variant	8/12	1	NM_030943.4	ENSP00000299155.6	Q9BXJ7-1
AMN	ENST00000559789.1 linkuse as main transcript	c.125-442A>G		intron_variant		3		ENSP00000452831.1	H0YKJ5
AMN	ENST00000541086.5 linkuse as main transcript	n.1575A>G		non_coding_transcript_exon_variant	7/11	2
AMN	ENST00000558590.1 linkuse as main transcript	n.792A>G		non_coding_transcript_exon_variant	3/9	2

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

GnomAD3 exomes

AF:

0.00496

AC:

766

AN:

154394

Hom.:

AF XY:

0.00527

AC XY:

434

AN XY:

82330

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 SAS exome

AF:

0.0105

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

Gnomad4 AFR exome

AF:

0.00101

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.000596

Gnomad4 EAS exome

AF:

0.0000279

Gnomad4 SAS exome

AF:

0.00897

Gnomad4 FIN exome

AF:

0.00135

Gnomad4 NFE exome

AF:

0.00713

Gnomad4 OTH exome

AF:

0.00608

GnomAD4 genome

AF:

0.00457

AC:

695

AN:

152030

Hom.:

Cov.:

AF XY:

0.00413

AC XY:

307

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.00696

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00600

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

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 18, 2020	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	AMN: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Imerslund-Grasbeck syndrome type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 09, 2023

- -

Imerslund-Grasbeck syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.24

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over