rs921072416

Variant summary

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

The NM_006750.4(SNTB2):​c.416C>A​(p.Pro139Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000723 in 1,383,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SNTB2
NM_006750.4 missense

Scores

7
9
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.47
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNTB2NM_006750.4 linkc.416C>A p.Pro139Gln missense_variant Exon 1 of 7 ENST00000336278.9 NP_006741.1 Q13425-1A0A024R732
SNTB2NR_172088.1 linkn.419C>A non_coding_transcript_exon_variant Exon 1 of 8
SNTB2NR_172089.1 linkn.419C>A non_coding_transcript_exon_variant Exon 1 of 7
SNTB2NR_172090.1 linkn.419C>A 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.416C>A p.Pro139Gln missense_variant Exon 1 of 7 1 NM_006750.4 ENSP00000338191.4 Q13425-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
7.23e-7
AC:
1
AN:
1383688
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
684914
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:
9.28e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.50
T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Benign
0.74
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Pathogenic
0.56
D
MetaRNN
Pathogenic
0.93
D
MetaSVM
Benign
-0.69
T
MutationAssessor
Uncertain
2.7
M
PrimateAI
Pathogenic
0.89
D
PROVEAN
Pathogenic
-6.3
D
REVEL
Uncertain
0.45
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.74
MutPred
0.76
Gain of MoRF binding (P = 0.035);
MVP
0.78
MPC
2.6
ClinPred
0.99
D
GERP RS
4.1
Varity_R
0.94
gMVP
0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-69221485; API