16-69187479-G-T

Variant summary

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

The NM_006750.4(SNTB2):​c.313G>T​(p.Gly105Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 1,223,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)
Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

SNTB2
NM_006750.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.668
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]
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]

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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=0.12809426).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNTB2NM_006750.4 linkc.313G>T p.Gly105Cys missense_variant Exon 1 of 7 ENST00000336278.9 NP_006741.1 Q13425-1A0A024R732
SNTB2NR_172088.1 linkn.316G>T non_coding_transcript_exon_variant Exon 1 of 8
SNTB2NR_172089.1 linkn.316G>T non_coding_transcript_exon_variant Exon 1 of 7
SNTB2NR_172090.1 linkn.316G>T non_coding_transcript_exon_variant Exon 1 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNTB2ENST00000336278.9 linkc.313G>T p.Gly105Cys missense_variant Exon 1 of 7 1 NM_006750.4 ENSP00000338191.4 Q13425-1
SNTB2ENST00000467311.5 linkn.313G>T non_coding_transcript_exon_variant Exon 1 of 6 1 ENSP00000436443.1 Q13425-2
UTP4ENST00000567287.2 linkn.82+20294G>T intron_variant Intron 1 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.00000673
AC:
1
AN:
148516
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000150
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
9.30e-7
AC:
1
AN:
1075338
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
508742
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:
0.0000349
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000673
AC:
1
AN:
148516
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
1
AN XY:
72328
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000150
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.313G>T (p.G105C) 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 313, causing the glycine (G) at amino acid position 105 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
0.14
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.30
T
Eigen
Benign
-0.98
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.40
T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.10
N
REVEL
Benign
0.021
Sift
Benign
0.051
T
Sift4G
Uncertain
0.052
T
Polyphen
0.085
B
Vest4
0.18
MutPred
0.28
Gain of glycosylation at P103 (P = 0.091);
MVP
0.42
MPC
1.6
ClinPred
0.33
T
GERP RS
1.2
Varity_R
0.11
gMVP
0.52

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.

Other links and lift over

dbSNP: rs749828433; hg19: chr16-69221382; API