Genetic Variant AMY1B:p.Leu328Ile (chr1-103691507-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001008218.2(AMY1B):c.982C>A(p.Leu328Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 1)

Exomes 𝑓: 0.000039 ( 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: 2.24

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13422558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMY1B	NM_001008218.2 link	c.982C>A	p.Leu328Ile	missense_variant	Exon 7 of 11	ENST00000330330.10	NP_001008219.1	P0DUB6P0DTE7P0DTE8
AMY1B	NM_001386925.1 link	c.982C>A	p.Leu328Ile	missense_variant	Exon 7 of 11		NP_001373854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMY1B	ENST00000330330.10 link	c.982C>A	p.Leu328Ile	missense_variant	Exon 7 of 11	1	NM_001008218.2	ENSP00000330484.5		P0DTE7
AMY1B	ENST00000370080.7 link	c.982C>A	p.Leu328Ile	missense_variant	Exon 7 of 11	2		ENSP00000359097.3		P0DTE7

Frequencies

GnomAD3 genomes

AF:

0.0000161

AC:

AN:

62212

Hom.:

Cov.:

show subpopulations

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:

0.000503

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000111

AC:

AN:

135650

Hom.:

AF XY:

0.000150

AC XY:

AN XY:

73380

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000744

Gnomad SAS exome

AF:

0.000875

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:

0.0000393

AC:

AN:

789080

Hom.:

Cov.:

AF XY:

0.0000610

AC XY:

AN XY:

393142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000319

Gnomad4 SAS exome

AF:

0.000573

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000506

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000161

AC:

AN:

62248

Hom.:

Cov.:

AF XY:

0.0000327

AC XY:

AN XY:

30548

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:

0.000505

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000131

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.982C>A (p.L328I) alteration is located in exon 7 (coding exon 6) of the AMY1B gene. This alteration results from a C to A substitution at nucleotide position 982, causing the leucine (L) at amino acid position 328 to be replaced by an isoleucine (I). 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

-0.26

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.91

.;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.13

T;T

MetaSVM

Pathogenic

0.96

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.3

N;N

REVEL

Uncertain

0.56

Sift

Benign

0.11

T;T

Sift4G

Benign

0.13

T;T

Vest4

0.33

MutPred

0.86

Gain of MoRF binding (P = 0.1692);Gain of MoRF binding (P = 0.1692);

MVP

0.16

ClinPred

0.097

GERP RS

2.1

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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