chr1-103691322-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 13/18 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
• 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 -4 ACMG points.

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

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.1073G>A	p.Arg358His	missense	Exon 8 of 11	NP_001008219.1	P0DTE7
	AMY1B	NM_001386925.1		c.1073G>A	p.Arg358His	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.1073G>A	p.Arg358His	missense	Exon 8 of 11	ENSP00000330484.5	P0DTE7
	AMY1B	ENST00000370080.7	TSL:2	c.1073G>A	p.Arg358His	missense	Exon 8 of 11	ENSP00000359097.3	P0DTE7
	AMY1B	ENST00000903269.1		c.1073G>A	p.Arg358His	missense	Exon 8 of 11	ENSP00000573328.1

Frequencies

GnomAD3 genomes AF: 0.000645 AC: 11 AN: 17062 Hom.: 0 Cov.: 0

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

GnomAD2 exomes AF: 0.000890 AC: 31 AN: 34828 AF XY: 0.000966

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000180

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000824

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00115

Gnomad OTH exome AF: 0.00168

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00131 AC: 7 AN: 5330

American (AMR) AF: 0.000276 AC: 5 AN: 18118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7128

East Asian (EAS) AF: 0.000396 AC: 9 AN: 22710

South Asian (SAS) AF: 0.00124 AC: 39 AN: 31376

European-Finnish (FIN) AF: 0.0000408 AC: 1 AN: 24536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1154

European-Non Finnish (NFE) AF: 0.000446 AC: 179 AN: 401086

Other (OTH) AF: 0.000826 AC: 17 AN: 20574

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000455 AC: 1 AN: 2198

American (AMR) AF: 0.000463 AC: 1 AN: 2160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 380

East Asian (EAS) AF: 0.00 AC: 0 AN: 988

South Asian (SAS) AF: 0.00909 AC: 3 AN: 330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.000526 AC: 5 AN: 9500

Other (OTH) AF: 0.00595 AC: 1 AN: 168

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00612493), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000169 Hom.: 0

ExAC AF: 0.000614 AC: 36

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	Benign	0.095
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
MetaSVM	Benign	-1.1	T
PhyloP100		2.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.089
Sift	Benign	0.28	T
Sift4G	Benign	0.14	T
Vest4		0.14
MutPred		0.43		Loss of sheet (P = 0.0104)
MVP		0.048
ClinPred		0.25	T
GERP RS		-0.24
gMVP		0.36
Mutation Taster		=97/3	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

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