1-103691507-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001008218.2(AMY1B):​c.982C>G​(p.Leu328Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L328I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 1)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AMY1B NM_001008218.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

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

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.37943286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMY1B	NM_001008218.2	c.982C>G	p.Leu328Val	missense_variant	Exon 7 of 11	ENST00000330330.10	NP_001008219.1
AMY1B	NM_001386925.1	c.982C>G	p.Leu328Val	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	c.982C>G	p.Leu328Val	missense_variant	Exon 7 of 11	1	NM_001008218.2	ENSP00000330484.5
AMY1B	ENST00000370080.7	c.982C>G	p.Leu328Val	missense_variant	Exon 7 of 11	2		ENSP00000359097.3

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 789090 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 393152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 1

ExAC AF: 0.0000263 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	0.0097	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Benign	0.97
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.38	T;T
MetaSVM	Pathogenic	0.90	D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.42
Sift	Benign	0.067	T;T
Sift4G	Benign	0.24	T;T
Vest4		0.31
MutPred		0.82		Gain of MoRF binding (P = 0.1131);Gain of MoRF binding (P = 0.1131);
MVP		0.20
ClinPred		0.79	D
GERP RS		2.1
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs577689111; hg19: chr1-104234129;