Variant rs921072416 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006750.4(SNTB2):c.416C>T(p.Pro139Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000847 in 1,534,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

SNTB2
NM_006750.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.47

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTB2	NM_006750.4 link	c.416C>T	p.Pro139Leu	missense_variant	Exon 1 of 7	ENST00000336278.9	NP_006741.1	Q13425-1A0A024R732
SNTB2	NR_172088.1 link	n.419C>T		non_coding_transcript_exon_variant	Exon 1 of 8
SNTB2	NR_172089.1 link	n.419C>T		non_coding_transcript_exon_variant	Exon 1 of 7
SNTB2	NR_172090.1 link	n.419C>T		non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTB2	ENST00000336278.9 link	c.416C>T	p.Pro139Leu	missense_variant	Exon 1 of 7	1	NM_006750.4	ENSP00000338191.4		Q13425-1

Frequencies

GnomAD3 genomes

AF:

0.0000397

AC:

AN:

151120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000971

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000506

AC:

AN:

1383686

Hom.:

Cov.:

AF XY:

0.00000438

AC XY:

AN XY:

684914

show subpopulations

Gnomad4 AFR exome

AF:

0.0000347

Gnomad4 AMR exome

AF:

0.00

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:

0.00000557

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000397

AC:

AN:

151120

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73800

show subpopulations

Gnomad4 AFR

AF:

0.0000971

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.416C>T (p.P139L) alteration is located in exon 1 (coding exon 1) of the SNTB2 gene. This alteration results from a C to T substitution at nucleotide position 416, causing the proline (P) at amino acid position 139 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.66

MetaRNN

Pathogenic

0.89

MetaSVM

Uncertain

-0.20

MutationAssessor

Pathogenic

3.0

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-8.1

REVEL

Uncertain

0.37

Sift

Uncertain

0.016

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.62

MVP

0.71

MPC

2.6

ClinPred

1.0

GERP RS

4.1

Varity_R

0.89

gMVP

0.88

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