Variant 1-103660431-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_004038.4(AMY1A):c.950A>G(p.Gln317Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000102 in 1,281,516 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 6 hom., cov: 17)

Exomes 𝑓: 0.00010 ( 36 hom. )

Failed GnomAD Quality Control

Consequence

AMY1A
NM_004038.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.82

Variant links:

Genes affected

AMY1A (HGNC:474): (amylase alpha 1A) Amylases are secreted proteins that hydrolyze 1,4-alpha-glucoside bonds in oligosaccharides and polysaccharides, and thus catalyze the first step in digestion of dietary starch and glycogen. The human genome has a cluster of several amylase genes that are expressed at high levels in either salivary gland or pancreas. This gene encodes an amylase isoenzyme produced by the salivary gland. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

AMY1A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.901

BS2

High Homozygotes in GnomAdExome4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMY1A	NM_004038.4 link	c.950A>G	p.Gln317Arg	missense_variant	7/11	ENST00000370083.9	NP_004029.2	P0DUB6P0DTE7P0DTE8Q6NSB3
AMY1A	NM_001008221.1 link	c.950A>G	p.Gln317Arg	missense_variant	7/11		NP_001008222.1	P0DUB6P0DTE7P0DTE8Q6NSB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMY1A	ENST00000370083.9 link	c.950A>G	p.Gln317Arg	missense_variant	7/11	1	NM_004038.4	ENSP00000359100.4		P0DUB6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

115058

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000168

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000256

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000755

AC:

AN:

211918

Hom.:

AF XY:

0.0000872

AC XY:

AN XY:

114720

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000264

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000821

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

131

AN:

1281516

Hom.:

Cov.:

AF XY:

0.0000896

AC XY:

AN XY:

636502

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000223

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.0000569

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000139

AC:

AN:

115058

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

55544

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000168

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000256

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000133

AC:

ExAC

AF:

0.0000819

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.950A>G (p.Q317R) alteration is located in exon 7 (coding exon 6) of the AMY1A gene. This alteration results from a A to G substitution at nucleotide position 950, causing the glutamine (Q) at amino acid position 317 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.79

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.85

M_CAP

Pathogenic

0.29

MetaRNN

Pathogenic

0.90

MetaSVM

Pathogenic

1.0

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.7

REVEL

Pathogenic

0.83

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.014

Polyphen

1.0

Vest4

0.80

MVP

0.92

MPC

3.5

ClinPred

0.61

GERP RS

2.4

Varity_R

0.71

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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