Variant chr14-102928749-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030943.4(AMN):c.296-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,605,570 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 Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

AMN
NM_030943.4 intron

Scores

Splicing: ADA: 0.03461

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.810

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
AMN	NM_030943.4 linkuse as main transcript	c.296-9C>G	intron_variant	ENST00000299155.10	NP_112205.2	Q9BXJ7-1
AMN	XM_011537202.4 linkuse as main transcript	c.134-9C>G	intron_variant			B3KP64
AMN	XM_011537203.4 linkuse as main transcript	c.134-9C>G	intron_variant		XP_011535505.1	B3KP64

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AMN	ENST00000299155.10 linkuse as main transcript	c.296-9C>G	intron_variant		1	NM_030943.4	ENSP00000299155.6	Q9BXJ7-1
AMN	ENST00000558590.1 linkuse as main transcript	n.105C>G	non_coding_transcript_exon_variant	1/9	2
AMN	ENST00000559442.1 linkuse as main transcript	n.58C>G	non_coding_transcript_exon_variant	1/3	2
AMN	ENST00000541086.5 linkuse as main transcript	n.1042-9C>G	intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000420

AC:

AN:

237820

Hom.:

AF XY:

0.0000538

AC XY:

AN XY:

130022

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.0000565

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000373

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000427

AC:

AN:

1453278

Hom.:

Cov.:

AF XY:

0.0000484

AC XY:

AN XY:

723008

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000350

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Imerslund-Grasbeck syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 20, 2022

This sequence change falls in intron 4 of the AMN gene. It does not directly change the encoded amino acid sequence of the AMN protein. This variant is present in population databases (rs373204347, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AMN-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.5

DANN

Benign

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.035

dbscSNV1_RF

Benign

0.13

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.31

Position offset: 9

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