Variant 1-103660445-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_004038.4(AMY1A):c.964G>A(p.Ala322Thr) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000043 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

AMY1A
NM_004038.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMY1A	NM_004038.4 linkuse as main transcript	c.964G>A	p.Ala322Thr	missense_variant	7/11	ENST00000370083.9	NP_004029.2	P0DUB6P0DTE7P0DTE8Q6NSB3
AMY1A	NM_001008221.1 linkuse as main transcript	c.964G>A	p.Ala322Thr	missense_variant	7/11		NP_001008222.1	P0DUB6P0DTE7P0DTE8Q6NSB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMY1A	ENST00000370083.9 linkuse as main transcript	c.964G>A	p.Ala322Thr	missense_variant	7/11	1	NM_004038.4	ENSP00000359100.4		P0DUB6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

117078

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000354

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000225

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000360

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000507

AC:

AN:

217070

Hom.:

AF XY:

0.0000512

AC XY:

AN XY:

117266

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000128

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:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000429

AC:

AN:

1283224

Hom.:

Cov.:

AF XY:

0.0000424

AC XY:

AN XY:

637396

show subpopulations

Gnomad4 AFR exome

AF:

0.000157

Gnomad4 AMR exome

AF:

0.000123

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000136

Gnomad4 SAS exome

AF:

0.0000694

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000356

Gnomad4 OTH exome

AF:

0.0000189

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000342

AC:

AN:

117108

Hom.:

Cov.:

AF XY:

0.0000706

AC XY:

AN XY:

56654

show subpopulations

Gnomad4 AFR

AF:

0.0000353

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000226

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000360

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000540

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

Aug 17, 2022

The c.964G>A (p.A322T) alteration is located in exon 7 (coding exon 6) of the AMY1A gene. This alteration results from a G to A substitution at nucleotide position 964, causing the alanine (A) at amino acid position 322 to be replaced by a threonine (T). 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

Benign

-0.18

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-0.66

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.26

Sift

Benign

0.093

Sift4G

Benign

0.061

Polyphen

1.0

Vest4

0.64

MutPred

0.58

Gain of disorder (P = 0.1419);

MVP

0.22

MPC

3.0

ClinPred

0.74

GERP RS

2.4

Varity_R

0.21

gMVP

0.29

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