Variant 8-120538968-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021021.4(SNTB1):c.1526A>G(p.Gln509Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,182 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SNTB1
NM_021021.4 missense, splice_region

Scores

Splicing: ADA: 0.9319

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01

Variant links:

Genes affected

SNTB1 (HGNC:11168): (syntrophin beta 1) 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]

SNTB1 links:

MTBP (HGNC:7417): (MDM2 binding protein) This gene encodes a protein that interacts with the oncoprotein mouse double minute 2. The encoded protein regulates progression through the cell cycle and may be involved in tumor formation. [provided by RefSeq, Aug 2012]

MTBP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SNTB1	NM_021021.4 linkuse as main transcript	c.1526A>G	p.Gln509Arg	missense_variant, splice_region_variant	7/7	ENST00000517992.2	NP_066301.1
SNTB1	XM_047422126.1 linkuse as main transcript	c.947A>G	p.Gln316Arg	missense_variant, splice_region_variant	7/7		XP_047278082.1
SNTB1	XM_047422127.1 linkuse as main transcript	c.947A>G	p.Gln316Arg	missense_variant, splice_region_variant	7/7		XP_047278083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNTB1	ENST00000517992.2 linkuse as main transcript	c.1526A>G	p.Gln509Arg	missense_variant, splice_region_variant	7/7	1	NM_021021.4	ENSP00000431124	P1	Q13884-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1455182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723852

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.1526A>G (p.Q509R) alteration is located in exon 7 (coding exon 7) of the SNTB1 gene. This alteration results from a A to G substitution at nucleotide position 1526, causing the glutamine (Q) at amino acid position 509 to be replaced by an arginine (R). 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

Benign

0.20

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

D;D

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.77

.;T

M_CAP

Benign

0.069

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Uncertain

0.075

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.5

N;N

REVEL

Uncertain

0.55

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.025

D;D

Polyphen

0.78

P;P

Vest4

0.72

MutPred

0.37

Loss of ubiquitination at K504 (P = 0.1268);Loss of ubiquitination at K504 (P = 0.1268);

MVP

0.79

ClinPred

0.94

GERP RS

5.8

Varity_R

0.47

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.93

dbscSNV1_RF

Pathogenic

0.82

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over