Genetic Variant AMY1B:p.Arg352Gln (chr1-103691340-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM1

The NM_001008218.2(AMY1B):c.1055G>A(p.Arg352Gln) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.000012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AMY1B
NM_001008218.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.44

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity AMY1B_HUMAN

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008218.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMY1B	NM_001008218.2	MANE Select	c.1055G>A	p.Arg352Gln	missense	Exon 8 of 11	NP_001008219.1	P0DTE7
	AMY1B	NM_001386925.1		c.1055G>A	p.Arg352Gln	missense	Exon 8 of 11	NP_001373854.1	P0DTE7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMY1B	ENST00000330330.10	TSL:1 MANE Select	c.1055G>A	p.Arg352Gln	missense	Exon 8 of 11	ENSP00000330484.5	P0DTE7
AMY1B	ENST00000370080.7	TSL:2	c.1055G>A	p.Arg352Gln	missense	Exon 8 of 11	ENSP00000359097.3	P0DTE7
AMY1B	ENST00000903269.1		c.1055G>A	p.Arg352Gln	missense	Exon 8 of 11	ENSP00000573328.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

42704

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000123

AC:

AN:

570562

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

285788

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

5868

American (AMR)

AF:

0.000103

AC:

AN:

19420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7902

East Asian (EAS)

AF:

0.00

AC:

AN:

24394

South Asian (SAS)

AF:

0.00

AC:

AN:

33522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1374

European-Non Finnish (NFE)

AF:

0.0000116

AC:

AN:

429642

Other (OTH)

AF:

0.00

AC:

AN:

22312

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000400382), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.346

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

Eigen

Benign

-0.011

Eigen_PC

Benign

-0.052

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.0076

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.81

PhyloP100

5.4

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.4

REVEL

Pathogenic

0.73

Sift

Benign

0.063

Sift4G

Benign

0.10

Vest4

0.50

MutPred

0.67

Loss of MoRF binding (P = 0.0237)

MVP

0.092

ClinPred

0.98

GERP RS

2.1

gMVP

0.57

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over