1-103573100-C-T

Variant names:

• chr1-103573100-C-T
• rs4098273
• NM_001387437.1:c.353C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001387437.1(AMY2B):​c.353C>T​(p.Ser118Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. S118C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AMY2B NM_001387437.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.49
• Publications: 0 publications found

Genes affected

AMY2B (HGNC:478): (amylase alpha 2B) 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 pancreas. [provided by RefSeq, Jun 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387437.1. 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
	AMY2B	NM_001387437.1	MANE Select	c.353C>T	p.Ser118Phe	missense	Exon 3 of 10	NP_001374366.1	P19961-1
	AMY2B	NM_001386109.1		c.353C>T	p.Ser118Phe	missense	Exon 5 of 12	NP_001373038.1	P19961-1
	AMY2B	NM_020978.4		c.353C>T	p.Ser118Phe	missense	Exon 5 of 12	NP_066188.1	P19961-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMY2B	ENST00000684275.1	MANE Select	c.353C>T	p.Ser118Phe	missense	Exon 3 of 10	ENSP00000507176.1	P19961-1
	AMY2B	ENST00000361355.8	TSL:1	c.353C>T	p.Ser118Phe	missense	Exon 5 of 12	ENSP00000354610.4	P19961-1
	AMY2B	ENST00000477657.5	TSL:2	n.353C>T		non_coding_transcript_exon	Exon 4 of 10	ENSP00000433347.1	P19961-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.79	D
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.61
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.28	B
Vest4		0.47
MutPred		0.57		Loss of disorder (P = 0.0137)
MVP		0.78
MPC		0.22
ClinPred		0.94	D
GERP RS		-1.1
Varity_R		0.23
gMVP		0.82
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs4098273; hg19: chr1-104115722;