Variant 1-103660401-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_004038.4(AMY1A):c.920C>T(p.Ala307Val) variant causes a missense change. The variant allele was found at a frequency of 0.00515 in 1,244,630 control chromosomes in the GnomAD database, including 1,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 43 hom., cov: 16)

Exomes 𝑓: 0.0051 ( 1413 hom. )

Failed GnomAD Quality Control

Consequence

AMY1A
NM_004038.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.67

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17515287).

BP6

Variant 1-103660401-C-T is Benign according to our data. Variant chr1-103660401-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 733787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 1413 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMY1A	NM_004038.4 linkuse as main transcript	c.920C>T	p.Ala307Val	missense_variant	7/11	ENST00000370083.9	NP_004029.2	P0DUB6P0DTE7P0DTE8Q6NSB3
AMY1A	NM_001008221.1 linkuse as main transcript	c.920C>T	p.Ala307Val	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.920C>T	p.Ala307Val	missense_variant	7/11	1	NM_004038.4	ENSP00000359100.4		P0DUB6

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

266

AN:

105414

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000860

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000642

Gnomad ASJ

AF:

0.000812

Gnomad EAS

AF:

0.000737

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000288

Gnomad MID

AF:

0.00397

Gnomad NFE

AF:

0.00449

Gnomad OTH

AF:

0.000735

GnomAD3 exomes

AF:

0.00237

AC:

390

AN:

164758

Hom.:

AF XY:

0.00240

AC XY:

213

AN XY:

88802

show subpopulations

Gnomad AFR exome

AF:

0.000894

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00126

Gnomad EAS exome

AF:

0.000277

Gnomad SAS exome

AF:

0.00230

Gnomad FIN exome

AF:

0.000439

Gnomad NFE exome

AF:

0.00406

Gnomad OTH exome

AF:

0.00153

GnomAD4 exome

AF:

0.00515

AC:

6408

AN:

1244630

Hom.:

1413

Cov.:

AF XY:

0.00520

AC XY:

3226

AN XY:

620062

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.000253

Gnomad4 ASJ exome

AF:

0.00234

Gnomad4 EAS exome

AF:

0.000164

Gnomad4 SAS exome

AF:

0.00256

Gnomad4 FIN exome

AF:

0.000661

Gnomad4 NFE exome

AF:

0.00625

Gnomad4 OTH exome

AF:

0.00302

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00252

AC:

266

AN:

105430

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

106

AN XY:

50554

show subpopulations

Gnomad4 AFR

AF:

0.000859

Gnomad4 AMR

AF:

0.000641

Gnomad4 ASJ

AF:

0.000812

Gnomad4 EAS

AF:

0.000740

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000288

Gnomad4 NFE

AF:

0.00449

Gnomad4 OTH

AF:

0.000726

Alfa

AF:

0.00295

Hom.:

ESP6500AA

AF:

0.000652

AC:

ESP6500EA

AF:

0.00334

AC:

ExAC

AF:

0.00287

AC:

302

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	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.82

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.18

MetaSVM

Pathogenic

1.1

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.3

REVEL

Pathogenic

0.80

Sift

Benign

0.078

Sift4G

Benign

0.065

Polyphen

1.0

Vest4

0.96

MVP

0.90

MPC

2.1

ClinPred

0.047

GERP RS

2.4

Varity_R

0.25

gMVP

0.49

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