Genetic Variant AMY2B:p.Phe3Leu (chr1-103571609-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001387437.1(AMY2B):c.7T>C(p.Phe3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,610,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

AMY2B
NM_001387437.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.159

Publications

1 publications found

Variant links:

Genes affected

AMY2B (HGNC:478): (amylase alpha 2B) 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 pancreas. [provided by RefSeq, Jun 2013]

AMY2B links:

ACTG1P4 (HGNC:149): (actin gamma 1 pseudogene 4)

ACTG1P4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028070182).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387437.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMY2B	NM_001387437.1	MANE Select	c.7T>C	p.Phe3Leu	missense	Exon 1 of 10	NP_001374366.1	P19961-1
AMY2B	NM_001386109.1		c.7T>C	p.Phe3Leu	missense	Exon 3 of 12	NP_001373038.1	P19961-1
AMY2B	NM_020978.4		c.7T>C	p.Phe3Leu	missense	Exon 3 of 12	NP_066188.1	P19961-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMY2B	ENST00000684275.1	MANE Select	c.7T>C	p.Phe3Leu	missense	Exon 1 of 10	ENSP00000507176.1	P19961-1
AMY2B	ENST00000361355.8	TSL:1	c.7T>C	p.Phe3Leu	missense	Exon 3 of 12	ENSP00000354610.4	P19961-1
AMY2B	ENST00000435302.5	TSL:3	c.7T>C	p.Phe3Leu	missense	Exon 3 of 4	ENSP00000391423.1	C9J2Z5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000173

AC:

AN:

230780

AF XY:

0.0000160

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000314

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000946

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1458774

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725490

show subpopulations

African (AFR)

AF:

0.0000599

AC:

AN:

33392

American (AMR)

AF:

0.0000224

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.00

AC:

AN:

86152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111030

Other (OTH)

AF:

0.00

AC:

AN:

60184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000869

Hom.:

ExAC

AF:

0.0000248

AC:

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

0.28

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.13

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.50

M_CAP

Benign

0.0011

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.24

PhyloP100

-0.16

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.010

REVEL

Benign

0.068

Sift

Benign

0.62

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.073

MutPred

0.22

Loss of ubiquitination at K2 (P = 0.0853)

MVP

0.18

MPC

0.15

ClinPred

0.016

GERP RS

0.40

PromoterAI

0.011

Neutral

(source)

Varity_R

0.029

gMVP

0.44

Mutation Taster

=95/5

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over