Variant chr1-103691518-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The ENST00000330330.10(AMY1B):c.971G>A(p.Gly324Glu) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000050 ( 0 hom., cov: 1)

Exomes 𝑓: 0.000064 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AMY1B
ENST00000330330.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.47

Variant links:

Genes affected

AMY1B (HGNC:475): (amylase alpha 1B) 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. [provided by RefSeq, Jul 2008]

AMY1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.971

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMY1B	NM_001008218.2 linkuse as main transcript	c.971G>A	p.Gly324Glu	missense_variant	7/11	ENST00000330330.10	NP_001008219.1
AMY1B	NM_001386925.1 linkuse as main transcript	c.971G>A	p.Gly324Glu	missense_variant	7/11		NP_001373854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMY1B	ENST00000330330.10 linkuse as main transcript	c.971G>A	p.Gly324Glu	missense_variant	7/11	1	NM_001008218.2	ENSP00000330484	P1
AMY1B	ENST00000370080.7 linkuse as main transcript	c.971G>A	p.Gly324Glu	missense_variant	7/11	2		ENSP00000359097	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

59878

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000962

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000470

AC:

AN:

127776

Hom.:

AF XY:

0.0000289

AC XY:

AN XY:

69180

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000643

AC:

AN:

761862

Hom.:

Cov.:

AF XY:

0.0000683

AC XY:

AN XY:

380668

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000664

Gnomad4 OTH exome

AF:

0.000354

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000501

AC:

AN:

59878

Hom.:

Cov.:

AF XY:

0.0000341

AC XY:

AN XY:

29294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000962

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000138

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

Dec 13, 2021

The c.971G>A (p.G324E) alteration is located in exon 7 (coding exon 6) of the AMY1B gene. This alteration results from a G to A substitution at nucleotide position 971, causing the glycine (G) at amino acid position 324 to be replaced by a glutamic acid (E). 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

Uncertain

0.057

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Benign

0.019

Eigen_PC

Benign

-0.046

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

.;D

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Benign

-0.49

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-6.7

D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.0080

D;D

Sift4G

Pathogenic

0.0010

D;D

Vest4

0.93

MutPred

0.89

Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);

MVP

0.21

ClinPred

0.66

GERP RS

2.1

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