Variant rs1034652574 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006750.4(SNTB2):c.286C>G(p.Pro96Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000979 in 1,021,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 9.8e-7 ( 0 hom. )

Consequence

SNTB2
NM_006750.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0400

Variant links:

Genes affected

SNTB2 (HGNC:11169): (syntrophin beta 2) Dystrophin is a large, rod-like cytoskeletal protein found at the inner surface of muscle fibers. Dystrophin is missing in Duchenne Muscular Dystrophy patients and is present in reduced amounts in Becker Muscular Dystrophy patients. The protein encoded by this gene is a peripheral membrane protein found associated with dystrophin and dystrophin-related proteins. This gene is a member of the syntrophin gene family, which contains at least two other structurally-related genes. [provided by RefSeq, Jul 2008]

SNTB2 links:

UTP4 (HGNC:1983): (UTP4 small subunit processome component) This gene encodes a WD40-repeat-containing protein that is localized to the nucleolus. Mutation of this gene causes North American Indian childhood cirrhosis, a severe intrahepatic cholestasis that results in transient neonatal jaundice, and progresses to periportal fibrosis and cirrhosis in childhood and adolescence. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

UTP4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12067449).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTB2	NM_006750.4 link	c.286C>G	p.Pro96Ala	missense_variant	Exon 1 of 7	ENST00000336278.9	NP_006741.1	Q13425-1A0A024R732
SNTB2	NR_172088.1 link	n.289C>G		non_coding_transcript_exon_variant	Exon 1 of 8
SNTB2	NR_172089.1 link	n.289C>G		non_coding_transcript_exon_variant	Exon 1 of 7
SNTB2	NR_172090.1 link	n.289C>G		non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SNTB2	ENST00000336278.9 link	c.286C>G	p.Pro96Ala	missense_variant	Exon 1 of 7	1	NM_006750.4	ENSP00000338191.4	Q13425-1
SNTB2	ENST00000467311.5 link	n.286C>G		non_coding_transcript_exon_variant	Exon 1 of 6	1		ENSP00000436443.1	Q13425-2
UTP4	ENST00000567287.2 link	n.82+20267C>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.79e-7

AC:

AN:

1021264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

481412

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000156

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.30

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.65

M_CAP

Benign

0.080

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.53

REVEL

Benign

0.061

Sift

Benign

0.31

Sift4G

Benign

0.63

Polyphen

0.46

Vest4

0.16

MutPred

0.29

Loss of catalytic residue at P96 (P = 0.0048);

MVP

0.54

MPC

1.5

ClinPred

0.31

GERP RS

5.0

Varity_R

0.066

gMVP

0.48

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over