Genetic Variant AMN:c.-87C>G (chr14-102922602-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030943.4(AMN):c.-87C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,493,412 control chromosomes in the GnomAD database, including 15,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 5467 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10221 hom. )

Consequence

AMN
NM_030943.4 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.04

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:

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 (BayesDel_noAF=-0.82).

BP6

Variant 14-102922602-C-G is Benign according to our data. Variant chr14-102922602-C-G is described in ClinVar as [Benign]. Clinvar id is 1286303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMN	NM_030943.4 link	c.-87C>G		upstream_gene_variant		ENST00000299155.10	NP_112205.2	Q9BXJ7-1
AMN	NM_001425246.1 link	c.-268C>G		upstream_gene_variant			NP_001412175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10 link	c.-87C>G		upstream_gene_variant		1	NM_030943.4	ENSP00000299155.6		Q9BXJ7-1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30883

AN:

151948

Hom.:

5442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.475

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.0936

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0736

Gnomad FIN

AF:

0.0945

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.170

GnomAD4 exome

AF:

0.105

AC:

141322

AN:

1341346

Hom.:

10221

AF XY:

0.103

AC XY:

68396

AN XY:

661784

show subpopulations

Gnomad4 AFR exome

AF:

0.490

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.0967

Gnomad4 EAS exome

AF:

0.000901

Gnomad4 SAS exome

AF:

0.0798

Gnomad4 FIN exome

AF:

0.0940

Gnomad4 NFE exome

AF:

0.0991

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.204

AC:

30962

AN:

152066

Hom.:

5467

Cov.:

AF XY:

0.199

AC XY:

14776

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.475

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.0936

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0729

Gnomad4 FIN

AF:

0.0945

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.0527

Hom.:

Bravo

AF:

0.221

Asia WGS

AF:

0.0700

AC:

245

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.7

DANN

Benign

0.75

Splicing

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