rs121912612

Positions:

• chr3-165069101-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_001041.4(SI):​c.350A>G​(p.Gln117Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SI NM_001041.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.109

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-165069101-T-C is Pathogenic according to our data. Variant chr3-165069101-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 1414.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.35381895). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SI	NM_001041.4	c.350A>G	p.Gln117Arg	missense_variant	4/48	ENST00000264382.8	NP_001032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SI	ENST00000264382.8	c.350A>G	p.Gln117Arg	missense_variant	4/48	1	NM_001041.4	ENSP00000264382	P1
SI	ENST00000476593.1	c.*225A>G		3_prime_UTR_variant, NMD_transcript_variant	4/5	4		ENSP00000419450

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Sucrase-isomaltase deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 29, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	2.1
DANN	Benign	0.94
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.79	N
MutationTaster	Benign	1.6e-12	A
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.54
Sift	Benign	0.31	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.056
MutPred		0.38		Loss of glycosylation at T121 (P = 0.0577);
MVP		0.71
MPC		0.030
ClinPred		0.11	T
GERP RS		0.46
Varity_R		0.13
gMVP		0.40

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: rs121912612; hg19: chr3-164786889;