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GeneBe

8-120541845-G-C

Variant summary

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

The NM_021021.4(SNTB1):c.1489C>G(p.Leu497Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000707 in 1,613,272 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

SNTB1
NM_021021.4 missense

Scores

3
13
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.29
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]
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]

Genome browser will be placed here

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, 0.86

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SNTB1NM_021021.4 linkuse as main transcriptc.1489C>G p.Leu497Val missense_variant 6/7 ENST00000517992.2
SNTB1XM_047422126.1 linkuse as main transcriptc.910C>G p.Leu304Val missense_variant 6/7
SNTB1XM_047422127.1 linkuse as main transcriptc.910C>G p.Leu304Val missense_variant 6/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SNTB1ENST00000517992.2 linkuse as main transcriptc.1489C>G p.Leu497Val missense_variant 6/71 NM_021021.4 P1Q13884-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152108
Hom.:
0
Cov.:
32
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
250722
Hom.:
0
AF XY:
0.0000443
AC XY:
6
AN XY:
135470
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000617
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000746
AC:
109
AN:
1461164
Hom.:
0
Cov.:
30
AF XY:
0.0000853
AC XY:
62
AN XY:
726824
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:
0.0000963
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152108
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74308
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:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsApr 21, 2022The c.1489C>G (p.L497V) alteration is located in exon 6 (coding exon 6) of the SNTB1 gene. This alteration results from a C to G substitution at nucleotide position 1489, causing the leucine (L) at amino acid position 497 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
Benign
0.33
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
0.10
Cadd
Uncertain
24
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.57
D;D
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.86
D;D
MetaSVM
Uncertain
0.60
D
MutationAssessor
Uncertain
2.7
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-2.5
N;N
REVEL
Pathogenic
0.65
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
1.0
D;D
Vest4
0.87
MVP
0.64
ClinPred
0.65
D
GERP RS
4.5
Varity_R
0.55
gMVP
0.61

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: rs371716468; hg19: chr8-121554085; API