3-165067458-G-C

Position:

chr3-165067458-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001041.4(SI):c.517C>G(p.Pro173Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,610,858 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 38 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 32 hom. )

Consequence

SI
NM_001041.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 8.26

Variant links:

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 links:

SI (HGNC:):

SI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009579778).

BP6

Variant 3-165067458-G-C is Benign according to our data. Variant chr3-165067458-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 445929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1928/152038) while in subpopulation AFR AF= 0.0439 (1819/41480). AF 95% confidence interval is 0.0422. There are 38 homozygotes in gnomad4. There are 941 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SI	NM_001041.4 linkuse as main transcript	c.517C>G	p.Pro173Ala	missense_variant	6/48	ENST00000264382.8	NP_001032.2	P14410

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SI	ENST00000264382.8 linkuse as main transcript	c.517C>G	p.Pro173Ala	missense_variant	6/48	1	NM_001041.4	ENSP00000264382.3		P14410

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1915

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0437

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00519

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00341

AC:

857

AN:

251150

Hom.:

AF XY:

0.00247

AC XY:

335

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.0455

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00127

AC:

1853

AN:

1458820

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

783

AN XY:

725920

show subpopulations

Gnomad4 AFR exome

AF:

0.0437

Gnomad4 AMR exome

AF:

0.00288

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000901

Gnomad4 OTH exome

AF:

0.00231

GnomAD4 genome

AF:

0.0127

AC:

1928

AN:

152038

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

941

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0439

Gnomad4 AMR

AF:

0.00518

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.000947

Hom.:

Bravo

AF:

0.0143

ESP6500AA

AF:

0.0452

AC:

199

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00413

AC:

502

Asia WGS

AF:

0.00348

AC:

AN:

3466

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 27, 2017	- -

Sucrase-isomaltase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Oct 12, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0096

MetaSVM

Uncertain

-0.27

MutationAssessor

Pathogenic

4.1

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.8

REVEL

Uncertain

0.36

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.83

MVP

0.87

MPC

0.14

ClinPred

0.064

GERP RS

4.9

Varity_R

0.70

gMVP

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over