Variant chr14-102923017-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030943.4(AMN):c.43+286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 449,526 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 13 hom., cov: 33)

Exomes 𝑓: 0.012 ( 36 hom. )

Consequence

AMN
NM_030943.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.519

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=-0.79).

BP6

Variant 14-102923017-T-C is Benign according to our data. Variant chr14-102923017-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1209347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0111 (1683/152296) while in subpopulation NFE AF= 0.0162 (1104/68020). AF 95% confidence interval is 0.0154. There are 13 homozygotes in gnomad4. There are 819 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
AMN	NM_030943.4 linkuse as main transcript	c.43+286T>C	intron_variant	ENST00000299155.10
AMN	XM_011537202.4 linkuse as main transcript	c.-120+267T>C	intron_variant
AMN	XM_011537203.4 linkuse as main transcript		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMN	ENST00000299155.10 linkuse as main transcript	c.43+286T>C		intron_variant		1	NM_030943.4	P1	Q9BXJ7-1
AMN	ENST00000541086.5 linkuse as main transcript	n.96T>C		non_coding_transcript_exon_variant	1/11	2

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1683

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00347

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.0148

GnomAD4 exome

AF:

0.0123

AC:

3655

AN:

297230

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

1861

AN XY:

156264

show subpopulations

Gnomad4 AFR exome

AF:

0.00382

Gnomad4 AMR exome

AF:

0.0151

Gnomad4 ASJ exome

AF:

0.00518

Gnomad4 EAS exome

AF:

0.0000527

Gnomad4 SAS exome

AF:

0.00549

Gnomad4 FIN exome

AF:

0.00895

Gnomad4 NFE exome

AF:

0.0157

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0111

AC:

1683

AN:

152296

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

819

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00346

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00932

Gnomad4 FIN

AF:

0.0125

Gnomad4 NFE

AF:

0.0162

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 21, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.1

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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