Variant 1-103691322-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001008218.2(AMY1B):c.1073G>A(p.Arg358His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00048 ( 7 hom. )

Failed GnomAD Quality Control

Consequence

AMY1B
NM_001008218.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.23

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010156244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMY1B	NM_001008218.2 linkuse as main transcript	c.1073G>A	p.Arg358His	missense_variant	8/11	ENST00000330330.10	NP_001008219.1	P0DUB6P0DTE7P0DTE8
AMY1B	NM_001386925.1 linkuse as main transcript	c.1073G>A	p.Arg358His	missense_variant	8/11		NP_001373854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMY1B	ENST00000330330.10 linkuse as main transcript	c.1073G>A	p.Arg358His	missense_variant	8/11	1	NM_001008218.2	ENSP00000330484.5		P0DTE7
AMY1B	ENST00000370080.7 linkuse as main transcript	c.1073G>A	p.Arg358His	missense_variant	8/11	2		ENSP00000359097.3		P0DTE7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

17062

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000463

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00920

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000526

Gnomad OTH

AF:

0.00610

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000483

AC:

257

AN:

532012

Hom.:

Cov.:

AF XY:

0.000504

AC XY:

134

AN XY:

266064

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.000276

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000396

Gnomad4 SAS exome

AF:

0.00124

Gnomad4 FIN exome

AF:

0.0000408

Gnomad4 NFE exome

AF:

0.000446

Gnomad4 OTH exome

AF:

0.000826

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000644

AC:

AN:

17086

Hom.:

Cov.:

AF XY:

0.000614

AC XY:

AN XY:

8138

show subpopulations

Gnomad4 AFR

AF:

0.000455

Gnomad4 AMR

AF:

0.000463

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00909

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000526

Gnomad4 OTH

AF:

0.00595

Alfa

AF:

0.000169

Hom.:

ExAC

AF:

0.000614

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

May 17, 2023

The c.1073G>A (p.R358H) alteration is located in exon 8 (coding exon 7) of the AMY1B gene. This alteration results from a G to A substitution at nucleotide position 1073, causing the arginine (R) at amino acid position 358 to be replaced by a histidine (H). 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

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.45

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.93

.;D

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.089

Sift

Benign

0.28

T;T

Sift4G

Benign

0.14

T;T

Vest4

0.14

MutPred

0.43

Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);

MVP

0.048

ClinPred

0.25

GERP RS

-0.24

gMVP

0.36

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