rs145227457

Variant names:

• chr3-164979047-TA-T
• rs145227457
• NM_001041.4:c.*314delT

Your query was ambiguous. Multiple possible variants found:

• chr3-164979047-TA-T
• chr3-164979047-TA-TAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001041.4(SI):​c.*314delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 180,896 control chromosomes in the GnomAD database, including 1,372 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1155 hom., cov: 30)
  • Exomes 𝑓: 0.11 (217 hom.)
• Consequence: SI NM_001041.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.32
• Publications: 1 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: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-164979047-TA-T is Benign according to our data. Variant chr3-164979047-TA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 343995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

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.*314delT		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.*314delT		3_prime_UTR	Exon 48 of 48	ENSP00000264382.3	P14410

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18058 AN: 151566 Hom.: 1154 Cov.: 30

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.0838

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0610

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.112 AC: 3278 AN: 29214 Hom.: 217 Cov.: 0 AF XY: 0.115 AC XY: 1822 AN XY: 15896

African (AFR) AF: 0.122 AC: 113 AN: 924

American (AMR) AF: 0.0614 AC: 123 AN: 2004

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 124 AN: 994

East Asian (EAS) AF: 0.0581 AC: 131 AN: 2256

South Asian (SAS) AF: 0.156 AC: 245 AN: 1574

European-Finnish (FIN) AF: 0.0916 AC: 57 AN: 622

Middle Eastern (MID) AF: 0.157 AC: 17 AN: 108

European-Non Finnish (NFE) AF: 0.120 AC: 2283 AN: 18956

Other (OTH) AF: 0.104 AC: 185 AN: 1776

GnomAD4 genome AF: 0.119 AC: 18067 AN: 151682 Hom.: 1155 Cov.: 30 AF XY: 0.114 AC XY: 8474 AN XY: 74146

African (AFR) AF: 0.134 AC: 5545 AN: 41450

American (AMR) AF: 0.0837 AC: 1271 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 401 AN: 3464

East Asian (EAS) AF: 0.0609 AC: 315 AN: 5170

South Asian (SAS) AF: 0.157 AC: 755 AN: 4818

European-Finnish (FIN) AF: 0.0585 AC: 618 AN: 10556

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8688 AN: 67730

Other (OTH) AF: 0.118 AC: 247 AN: 2096

Alfa AF: 0.124 Hom.: 136

Bravo AF: 0.120

Asia WGS AF: 0.109 AC: 374 AN: 3432

ClinVar

ClinVar submissions as Germline

Significance: Likely 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
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs145227457; hg19: chr3-164696835;