1-103691322-C-T

Variant names:

• chr1-103691322-C-T
• rs541141393
• NM_001008218.2:c.1073G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001008218.2(AMY1B):​c.1073G>A​(p.Arg358His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00048 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: AMY1B NM_001008218.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010156244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMY1B	NM_001008218.2	c.1073G>A	p.Arg358His	missense_variant	Exon 8 of 11	ENST00000330330.10	NP_001008219.1
AMY1B	NM_001386925.1	c.1073G>A	p.Arg358His	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.1073G>A	p.Arg358His	missense_variant	Exon 8 of 11	1	NM_001008218.2	ENSP00000330484.5
AMY1B	ENST00000370080.7	c.1073G>A	p.Arg358His	missense_variant	Exon 8 of 11	2		ENSP00000359097.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 11 AN: 17062 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000463

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00920

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000526

Gnomad OTH AF: 0.00610

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000483 AC: 257 AN: 532012 Hom.: 7 Cov.: 5 AF XY: 0.000504 AC XY: 134 AN XY: 266064

Gnomad4 AFR exome AF: 0.00131

Gnomad4 AMR exome AF: 0.000276

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000396

Gnomad4 SAS exome AF: 0.00124

Gnomad4 FIN exome AF: 0.0000408

Gnomad4 NFE exome AF: 0.000446

Gnomad4 OTH exome AF: 0.000826

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000644 AC: 11 AN: 17086 Hom.: 0 Cov.: 0 AF XY: 0.000614 AC XY: 5 AN XY: 8138

Gnomad4 AFR AF: 0.000455

Gnomad4 AMR AF: 0.000463

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00909

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000526

Gnomad4 OTH AF: 0.00595

Alfa AF: 0.000169 Hom.: 0

ExAC AF: 0.000614 AC: 36

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1073G>A (p.R358H) 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 1073, causing the arginine (R) at amino acid position 358 to be replaced by a histidine (H). 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	Benign	-0.58	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Benign	0.45
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.93	.;D
MetaRNN	Benign	0.010	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.089
Sift	Benign	0.28	T;T
Sift4G	Benign	0.14	T;T
Vest4		0.14
MutPred		0.43		Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);
MVP		0.048
ClinPred		0.25	T
GERP RS		-0.24
gMVP		0.36

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: rs541141393; hg19: chr1-104233944; COSMIC: COSV100375562; COSMIC: COSV100375562;