1-103691507-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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: Uncertain_significance. The variant received 1 ACMG points.

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

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>T	p.Leu328Phe	missense	Exon 7 of 11	NP_001008219.1	P0DTE7
	AMY1B	NM_001386925.1		c.982C>T	p.Leu328Phe	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>T	p.Leu328Phe	missense	Exon 7 of 11	ENSP00000330484.5	P0DTE7
	AMY1B	ENST00000370080.7	TSL:2	c.982C>T	p.Leu328Phe	missense	Exon 7 of 11	ENSP00000359097.3	P0DTE7
	AMY1B	ENST00000903269.1		c.982C>T	p.Leu328Phe	missense	Exon 7 of 11	ENSP00000573328.1

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD2 exomes AF: 0.00000737 AC: 1 AN: 135650 AF XY: 0.00

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 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

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: 0.00 AC: 0 AN: 31358

South Asian (SAS) AF: 0.00 AC: 0 AN: 47108

European-Finnish (FIN) AF: 0.0000606 AC: 2 AN: 33030

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 593304

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

GnomAD4 genome Cov.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
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
MetaSVM	Pathogenic	0.97	D
PhyloP100		2.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.2	D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Vest4		0.62
MutPred		0.83		Gain of helix (P = 0.1736)
MVP		0.25
ClinPred		0.98	D
GERP RS		2.1
gMVP		0.26
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs577689111; hg19: chr1-104234129;