16-69187587-C-G

Variant summary

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

The NM_006750.4(SNTB2):ā€‹c.421C>Gā€‹(p.Leu141Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000389 in 1,541,354 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000036 ( 0 hom. )

Consequence

SNTB2
NM_006750.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.76
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]

Genome browser will be placed here

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 rank MANE Protein UniProt
SNTB2NM_006750.4 linkc.421C>G p.Leu141Val missense_variant Exon 1 of 7 ENST00000336278.9 NP_006741.1 Q13425-1A0A024R732
SNTB2NR_172088.1 linkn.424C>G non_coding_transcript_exon_variant Exon 1 of 8
SNTB2NR_172089.1 linkn.424C>G non_coding_transcript_exon_variant Exon 1 of 7
SNTB2NR_172090.1 linkn.424C>G 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.421C>G p.Leu141Val missense_variant Exon 1 of 7 1 NM_006750.4 ENSP00000338191.4 Q13425-1

Frequencies

GnomAD3 genomes
AF:
0.00000661
AC:
1
AN:
151300
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:
0.00
Gnomad OTH
AF:
0.000480
GnomAD4 exome
AF:
0.00000360
AC:
5
AN:
1390054
Hom.:
0
Cov.:
31
AF XY:
0.00000291
AC XY:
2
AN XY:
688430
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:
0.00000278
Gnomad4 OTH exome
AF:
0.0000349
GnomAD4 genome
AF:
0.00000661
AC:
1
AN:
151300
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
73906
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:
0.00
Gnomad4 OTH
AF:
0.000480
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.421C>G (p.L141V) alteration is located in exon 1 (coding exon 1) of the SNTB2 gene. This alteration results from a C to G substitution at nucleotide position 421, causing the leucine (L) at amino acid position 141 to be replaced by a valine (V). 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
Uncertain
0.53
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
25
DANN
Benign
0.94
DEOGEN2
Benign
0.39
T
Eigen
Benign
0.17
Eigen_PC
Benign
0.22
FATHMM_MKL
Benign
0.52
D
LIST_S2
Uncertain
0.95
D
M_CAP
Uncertain
0.17
D
MetaRNN
Uncertain
0.45
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.39
N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.16
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0070
D
Polyphen
0.86
P
Vest4
0.41
MutPred
0.65
Gain of methylation at K144 (P = 0.0853);
MVP
0.62
MPC
1.9
ClinPred
0.72
D
GERP RS
4.0
Varity_R
0.79
gMVP
0.57

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: rs1293745604; hg19: chr16-69221490; API