rs1189968161

Variant names:

• chr1-103691340-C-T
• rs1189968161
• NM_001008218.2:c.1055G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1

The NM_001008218.2(AMY1B):​c.1055G>A​(p.Arg352Gln) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AMY1B NM_001008218.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44

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.

• PM1: In a binding_site (size 0) in uniprot entity AMY1B_HUMAN

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMY1B	NM_001008218.2	c.1055G>A	p.Arg352Gln	missense_variant	Exon 8 of 11	ENST00000330330.10	NP_001008219.1
AMY1B	NM_001386925.1	c.1055G>A	p.Arg352Gln	missense_variant	Exon 8 of 11		NP_001373854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMY1B	ENST00000330330.10	c.1055G>A	p.Arg352Gln	missense_variant	Exon 8 of 11	1	NM_001008218.2	ENSP00000330484.5
AMY1B	ENST00000370080.7	c.1055G>A	p.Arg352Gln	missense_variant	Exon 8 of 11	2		ENSP00000359097.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000123 AC: 7 AN: 570562 Hom.: 0 Cov.: 6 AF XY: 0.0000175 AC XY: 5 AN XY: 285788

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000103

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000116

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1055G>A (p.R352Q) alteration is located in exon 8 (coding exon 7) of the AMY1B gene. This alteration results from a G to A substitution at nucleotide position 1055, causing the arginine (R) at amino acid position 352 to be replaced by a glutamine (Q). 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	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Pathogenic	1.0
Eigen	Benign	-0.011
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.99	.;D
M_CAP	Benign	0.0076	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.81	T
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Pathogenic	0.73
Sift	Benign	0.063	T;T
Sift4G	Benign	0.10	T;T
Vest4		0.50
MutPred		0.67		Loss of MoRF binding (P = 0.0237);Loss of MoRF binding (P = 0.0237);
MVP		0.092
ClinPred		0.98	D
GERP RS		2.1
gMVP		0.57

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: rs1189968161; hg19: chr1-104233962;