1-103691306-A-C

Variant names:

• chr1-103691306-A-C
• NM_001008218.2:c.1089T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001008218.2(AMY1B):​c.1089T>G​(p.Phe363Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: AMY1B NM_001008218.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93
• Publications: 0 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=0.17782843).

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.1089T>G	p.Phe363Leu	missense	Exon 8 of 11	NP_001008219.1	P0DTE7
	AMY1B	NM_001386925.1		c.1089T>G	p.Phe363Leu	missense	Exon 8 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.1089T>G	p.Phe363Leu	missense	Exon 8 of 11	ENSP00000330484.5	P0DTE7
	AMY1B	ENST00000370080.7	TSL:2	c.1089T>G	p.Phe363Leu	missense	Exon 8 of 11	ENSP00000359097.3	P0DTE7
	AMY1B	ENST00000903269.1		c.1089T>G	p.Phe363Leu	missense	Exon 8 of 11	ENSP00000573328.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 0

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	Pathogenic	0.59
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.87
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.95	T
PhyloP100		1.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.19
Sift	Benign	0.32	T
Sift4G	Uncertain	0.028	D
Vest4		0.34
MutPred		0.61		Gain of MoRF binding (P = 0.1228)
MVP		0.030
ClinPred		0.57	D
GERP RS		0.88
gMVP		0.27
Mutation Taster		=95/5	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

hg19: chr1-104233928;