3-164979294-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001041.4(SI):c.*68T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 922,226 control chromosomes in the GnomAD database, including 17,661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (7814 hom., cov: 32)
  • Exomes 𝑓: 0.14 (9847 hom.)
• Consequence: SI NM_001041.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.922

Genes affected

SI (HGNC:10856): (sucrase-isomaltase) This gene encodes a sucrase-isomaltase enzyme that is expressed in the intestinal brush border. The encoded protein is synthesized as a precursor protein that is cleaved by pancreatic proteases into two enzymatic subunits sucrase and isomaltase. These two subunits heterodimerize to form the sucrose-isomaltase complex. This complex is essential for the digestion of dietary carbohydrates including starch, sucrose and isomaltose. Mutations in this gene are the cause of congenital sucrase-isomaltase deficiency.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-164979294-A-G is Benign according to our data. Variant chr3-164979294-A-G is described in ClinVar as [Benign]. Clinvar id is 343998.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SI	NM_001041.4	c.*68T>C		3_prime_UTR_variant	48/48	ENST00000264382.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SI	ENST00000264382.8	c.*68T>C		3_prime_UTR_variant	48/48	1	NM_001041.4	P1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37126 AN: 151440 Hom.: 7785 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0635

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.137 AC: 105394 AN: 770668 Hom.: 9847 Cov.: 10 AF XY: 0.138 AC XY: 56610 AN XY: 410454

Gnomad4 AFR exome AF: 0.576

Gnomad4 AMR exome AF: 0.0838

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.0652

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.0679

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.245 AC: 37205 AN: 151558 Hom.: 7814 Cov.: 32 AF XY: 0.236 AC XY: 17475 AN XY: 74058

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0635

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.0597

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.200

Alfa AF: 0.177 Hom.: 796

Bravo AF: 0.264

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Sucrase-isomaltase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.34
Dann	Benign	0.37

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: rs73018867; hg19: chr3-164697082; COSMIC: COSV52274208;