rs577689111

Variant names:

• chr1-103691507-G-T
• rs577689111
• NM_001008218.2:c.982C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-103691507-G-T
• chr1-103691507-G-A
• chr1-103691507-G-C

Variant summary

Our verdict is Likely benign. The variant received -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. 12/20 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24
• Publications: 1 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.13422558).

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.982C>A	p.Leu328Ile	missense	Exon 7 of 11	NP_001008219.1	P0DTE7
	AMY1B	NM_001386925.1		c.982C>A	p.Leu328Ile	missense	Exon 7 of 11	NP_001373854.1	P0DTE7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMY1B	ENST00000330330.10	TSL:1 MANE Select	c.982C>A	p.Leu328Ile	missense	Exon 7 of 11	ENSP00000330484.5	P0DTE7
	AMY1B	ENST00000370080.7	TSL:2	c.982C>A	p.Leu328Ile	missense	Exon 7 of 11	ENSP00000359097.3	P0DTE7
	AMY1B	ENST00000903269.1		c.982C>A	p.Leu328Ile	missense	Exon 7 of 11	ENSP00000573328.1

Frequencies

GnomAD3 genomes AF: 0.0000161 AC: 1 AN: 62212 Hom.: 0 Cov.: 1

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

GnomAD2 exomes AF: 0.000111 AC: 15 AN: 135650 AF XY: 0.000150

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 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: 31 AN: 789080 Hom.: 0 Cov.: 22 AF XY: 0.0000610 AC XY: 24 AN XY: 393142

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

African (AFR) AF: 0.00 AC: 0 AN: 9600

American (AMR) AF: 0.00 AC: 0 AN: 27762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12404

East Asian (EAS) AF: 0.0000319 AC: 1 AN: 31358

South Asian (SAS) AF: 0.000573 AC: 27 AN: 47098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2468

European-Non Finnish (NFE) AF: 0.00000506 AC: 3 AN: 593304

Other (OTH) AF: 0.00 AC: 0 AN: 32056

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000161 AC: 1 AN: 62248 Hom.: 0 Cov.: 1 AF XY: 0.0000327 AC XY: 1 AN XY: 30548

African (AFR) AF: 0.00 AC: 0 AN: 9610

American (AMR) AF: 0.00 AC: 0 AN: 6952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1446

East Asian (EAS) AF: 0.00 AC: 0 AN: 3410

South Asian (SAS) AF: 0.000505 AC: 1 AN: 1982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 90

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 32310

Other (OTH) AF: 0.00 AC: 0 AN: 768

ExAC AF: 0.000131 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Benign	0.95
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.13	T
MetaSVM	Pathogenic	0.96	D
PhyloP100		2.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.56
Sift	Benign	0.11	T
Sift4G	Benign	0.13	T
Vest4		0.33
MutPred		0.86		Gain of MoRF binding (P = 0.1692)
MVP		0.16
ClinPred		0.097	T
GERP RS		2.1
gMVP		0.11
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs577689111; hg19: chr1-104234129;