rs141455061

Positions:

chr14-102928825-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_030943.4(AMN):c.363G>A(p.Gly121Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00546 in 1,607,086 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 57 hom. )

Consequence

AMN
NM_030943.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.823

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 14-102928825-G-A is Benign according to our data. Variant chr14-102928825-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 532207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.823 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00588 (895/152340) while in subpopulation NFE AF= 0.00578 (393/68038). AF 95% confidence interval is 0.0053. There are 7 homozygotes in gnomad4. There are 542 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMN	NM_030943.4 linkuse as main transcript	c.363G>A	p.Gly121Gly	synonymous_variant	5/12	ENST00000299155.10	NP_112205.2	Q9BXJ7-1
AMN	XM_011537202.4 linkuse as main transcript	c.201G>A	p.Gly67Gly	synonymous_variant	5/12			B3KP64
AMN	XM_011537203.4 linkuse as main transcript	c.201G>A	p.Gly67Gly	synonymous_variant	5/12		XP_011535505.1	B3KP64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10 linkuse as main transcript	c.363G>A	p.Gly121Gly	synonymous_variant	5/12	1	NM_030943.4	ENSP00000299155.6		Q9BXJ7-1

Frequencies

GnomAD3 genomes

AF:

0.00588

AC:

895

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0407

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00578

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00595

AC:

1451

AN:

243764

Hom.:

AF XY:

0.00575

AC XY:

764

AN XY:

132958

show subpopulations

Gnomad AFR exome

AF:

0.00100

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.000802

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.0369

Gnomad NFE exome

AF:

0.00619

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00542

AC:

7887

AN:

1454746

Hom.:

Cov.:

AF XY:

0.00523

AC XY:

3789

AN XY:

723984

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000917

Gnomad4 ASJ exome

AF:

0.000460

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000893

Gnomad4 FIN exome

AF:

0.0370

Gnomad4 NFE exome

AF:

0.00518

Gnomad4 OTH exome

AF:

0.00421

GnomAD4 genome

AF:

0.00588

AC:

895

AN:

152340

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

542

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0407

Gnomad4 NFE

AF:

0.00578

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00483

Hom.:

Bravo

AF:

0.00291

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00480

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2022	AMN: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 14, 2022	See Variant Classification Assertion Criteria. -

Imerslund-Grasbeck syndrome type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 02, 2023

- -

Imerslund-Grasbeck syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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