rs577689111

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_001008218.2(AMY1B):​c.982C>T​(p.Leu328Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic 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: 0.0000025 (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 Uncertain_significance. Variant got 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMY1B	NM_001008218.2	c.982C>T	p.Leu328Phe	missense_variant	Exon 7 of 11	ENST00000330330.10	NP_001008219.1
AMY1B	NM_001386925.1	c.982C>T	p.Leu328Phe	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>T	p.Leu328Phe	missense_variant	Exon 7 of 11	1	NM_001008218.2	ENSP00000330484.5
AMY1B	ENST00000370080.7	c.982C>T	p.Leu328Phe	missense_variant	Exon 7 of 11	2		ENSP00000359097.3

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD3 exomes AF: 0.00000737 AC: 1 AN: 135650 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73380

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000752

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000253 AC: 2 AN: 789090 Hom.: 0 Cov.: 22 AF XY: 0.00000254 AC XY: 1 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: 0.0000606

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Pathogenic	0.97	D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.2	D;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Vest4		0.62
MutPred		0.83		Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);
MVP		0.25
ClinPred		0.98	D
GERP RS		2.1
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs577689111; hg19: chr1-104234129;