Variant chr16-69187395-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006750.4(SNTB2):c.229G>T(p.Gly77Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000504 in 1,274,190 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00053 ( 1 hom. )

Consequence

SNTB2
NM_006750.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

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:

SNTB2 (HGNC:):

SNTB2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03595099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNTB2	NM_006750.4 linkuse as main transcript	c.229G>T	p.Gly77Cys	missense_variant	1/7	ENST00000336278.9	NP_006741.1	Q13425-1A0A024R732
SNTB2	NR_172088.1 linkuse as main transcript	n.232G>T		non_coding_transcript_exon_variant	1/8
SNTB2	NR_172089.1 linkuse as main transcript	n.232G>T		non_coding_transcript_exon_variant	1/7
SNTB2	NR_172090.1 linkuse as main transcript	n.232G>T		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SNTB2	ENST00000336278.9 linkuse as main transcript	c.229G>T	p.Gly77Cys	missense_variant	1/7	1	NM_006750.4	ENSP00000338191.4	Q13425-1
SNTB2	ENST00000467311.5 linkuse as main transcript	n.229G>T		non_coding_transcript_exon_variant	1/6	1		ENSP00000436443.1	Q13425-2
UTP4	ENST00000567287.2 linkuse as main transcript	n.82+20210G>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000301

AC:

AN:

149290

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000210

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000462

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000878

AC:

AN:

3418

Hom.:

AF XY:

0.00126

AC XY:

AN XY:

2372

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad SAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000531

AC:

597

AN:

1124900

Hom.:

Cov.:

AF XY:

0.000567

AC XY:

308

AN XY:

542952

show subpopulations

Gnomad4 AFR exome

AF:

0.000132

Gnomad4 AMR exome

AF:

0.000468

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000353

Gnomad4 FIN exome

AF:

0.000129

Gnomad4 NFE exome

AF:

0.000592

Gnomad4 OTH exome

AF:

0.000313

GnomAD4 genome

AF:

0.000301

AC:

AN:

149290

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

72808

show subpopulations

Gnomad4 AFR

AF:

0.000219

Gnomad4 AMR

AF:

0.000133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000210

Gnomad4 NFE

AF:

0.000462

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000810

Hom.:

Bravo

AF:

0.000348

ExAC

AF:

0.0000850

AC:

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

Jun 21, 2023

The c.229G>T (p.G77C) alteration is located in exon 1 (coding exon 1) of the SNTB2 gene. This alteration results from a G to T substitution at nucleotide position 229, causing the glycine (G) at amino acid position 77 to be replaced by a cysteine (C). 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

0.12

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.5

REVEL

Benign

0.022

Sift

Uncertain

0.011

Sift4G

Uncertain

0.023

Polyphen

0.0030

Vest4

0.19

MVP

0.60

MPC

1.6

ClinPred

0.12

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.54

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