1-103691386-T-C

Position:

• chr1-103691386-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001008218.2(AMY1B):​c.1009A>G​(p.Lys337Glu) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 1)
• Consequence: AMY1B NM_001008218.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.23

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 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.88

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMY1B	NM_001008218.2	c.1009A>G	p.Lys337Glu	missense_variant	8/11	ENST00000330330.10	NP_001008219.1
AMY1B	NM_001386925.1	c.1009A>G	p.Lys337Glu	missense_variant	8/11		NP_001373854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMY1B	ENST00000330330.10	c.1009A>G	p.Lys337Glu	missense_variant	8/11	1	NM_001008218.2	ENSP00000330484.5
AMY1B	ENST00000370080.7	c.1009A>G	p.Lys337Glu	missense_variant	8/11	2		ENSP00000359097.3

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD4 exome Cov.: 5

GnomAD4 genome Cov.: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

The c.1009A>G (p.K337E) alteration is located in exon 8 (coding exon 7) of the AMY1B gene. This alteration results from a A to G substitution at nucleotide position 1009, causing the lysine (K) at amino acid position 337 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Benign	-0.010
Eigen_PC	Benign	-0.078
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Pathogenic	0.32	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Pathogenic	1.0	D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.7	D;D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.030	D;D
Vest4		0.64
MutPred		0.80		Loss of ubiquitination at K337 (P = 0.0326);Loss of ubiquitination at K337 (P = 0.0326);
MVP		0.26
ClinPred		0.97	D
GERP RS		2.1
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-104234008;