chr3-164979164-C-A

Variant names:

• chr3-164979164-C-A
• rs146143233
• NM_001041.4:c.*198G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001041.4(SI):​c.*198G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 548,436 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (6 hom.)
• Consequence: SI NM_001041.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.396
• Publications: 0 publications found

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]

SI Gene-Disease associations (from GenCC):

• congenital sucrase-isomaltase deficiency

  Inheritance: SD, AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-164979164-C-A is Benign according to our data. Variant chr3-164979164-C-A is described in ClinVar as Benign. ClinVar VariationId is 900516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00832 (1262/151654) while in subpopulation AFR AF = 0.0291 (1207/41458). AF 95% confidence interval is 0.0277. There are 22 homozygotes in GnomAd4. There are 597 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001041.4. 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
	SI	NM_001041.4	MANE Select	c.*198G>T		3_prime_UTR	Exon 48 of 48	NP_001032.2	P14410

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SI	ENST00000264382.8	TSL:1 MANE Select	c.*198G>T		3_prime_UTR	Exon 48 of 48	ENSP00000264382.3	P14410

Frequencies

GnomAD3 genomes AF: 0.00829 AC: 1256 AN: 151536 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00244

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00622

GnomAD4 exome AF: 0.00116 AC: 459 AN: 396782 Hom.: 6 Cov.: 2 AF XY: 0.000967 AC XY: 204 AN XY: 210986

African (AFR) AF: 0.0311 AC: 362 AN: 11634

American (AMR) AF: 0.00135 AC: 25 AN: 18496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12320

East Asian (EAS) AF: 0.00 AC: 0 AN: 28908

South Asian (SAS) AF: 0.000109 AC: 4 AN: 36596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25790

Middle Eastern (MID) AF: 0.000568 AC: 1 AN: 1762

European-Non Finnish (NFE) AF: 0.0000252 AC: 6 AN: 238110

Other (OTH) AF: 0.00263 AC: 61 AN: 23166

GnomAD4 genome AF: 0.00832 AC: 1262 AN: 151654 Hom.: 22 Cov.: 32 AF XY: 0.00806 AC XY: 597 AN XY: 74098

African (AFR) AF: 0.0291 AC: 1207 AN: 41458

American (AMR) AF: 0.00244 AC: 37 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67700

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00826 Hom.: 1

Bravo AF: 0.00930

Asia WGS AF: 0.00116 AC: 4 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Sucrase-isomaltase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		0.40
Mutation Taster		=100/0	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: rs146143233; hg19: chr3-164696952;