Variant 1-103660444-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004038.4(AMY1A):c.963C>T(p.Gly321Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00705 in 1,282,140 control chromosomes in the GnomAD database, including 2,067 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 65 hom., cov: 17)

Exomes 𝑓: 0.0070 ( 2067 hom. )

Failed GnomAD Quality Control

Consequence

AMY1A
NM_004038.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.01

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 Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 1-103660444-C-T is Benign according to our data. Variant chr1-103660444-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 711054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2067 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMY1A	NM_004038.4 linkuse as main transcript	c.963C>T	p.Gly321Gly	synonymous_variant	7/11	ENST00000370083.9	NP_004029.2	P0DUB6P0DTE7P0DTE8Q6NSB3
AMY1A	NM_001008221.1 linkuse as main transcript	c.963C>T	p.Gly321Gly	synonymous_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.963C>T	p.Gly321Gly	synonymous_variant	7/11	1	NM_004038.4	ENSP00000359100.4		P0DUB6

Frequencies

GnomAD3 genomes

AF:

0.00405

AC:

472

AN:

116628

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00131

Gnomad AMI

AF:

0.00597

Gnomad AMR

AF:

0.00265

Gnomad ASJ

AF:

0.0149

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.00413

Gnomad MID

AF:

0.00699

Gnomad NFE

AF:

0.00538

Gnomad OTH

AF:

0.00391

GnomAD3 exomes

AF:

0.00644

AC:

1396

AN:

216790

Hom.:

336

AF XY:

0.00692

AC XY:

811

AN XY:

117138

show subpopulations

Gnomad AFR exome

AF:

0.00189

Gnomad AMR exome

AF:

0.00360

Gnomad ASJ exome

AF:

0.0215

Gnomad EAS exome

AF:

0.0000592

Gnomad SAS exome

AF:

0.00988

Gnomad FIN exome

AF:

0.00403

Gnomad NFE exome

AF:

0.00736

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00705

AC:

9037

AN:

1282140

Hom.:

2067

Cov.:

AF XY:

0.00715

AC XY:

4551

AN XY:

636872

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00364

Gnomad4 ASJ exome

AF:

0.0170

Gnomad4 EAS exome

AF:

0.0000543

Gnomad4 SAS exome

AF:

0.00962

Gnomad4 FIN exome

AF:

0.00540

Gnomad4 NFE exome

AF:

0.00731

Gnomad4 OTH exome

AF:

0.00679

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00405

AC:

472

AN:

116658

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

237

AN XY:

56432

show subpopulations

Gnomad4 AFR

AF:

0.00131

Gnomad4 AMR

AF:

0.00265

Gnomad4 ASJ

AF:

0.0149

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00581

Gnomad4 FIN

AF:

0.00413

Gnomad4 NFE

AF:

0.00538

Gnomad4 OTH

AF:

0.00386

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	AMY1A: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.0

DANN

Benign

0.59

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