16-69187231-C-T

Variant names:

Variant summary

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

The NM_006750.4(SNTB2):c.65C>T(p.Ala22Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,452,698 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SNTB2
NM_006750.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.18

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:

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]

UTP4 links:

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
SNTB2	NM_006750.4 link	c.65C>T	p.Ala22Val	missense_variant	Exon 1 of 7	ENST00000336278.9	NP_006741.1	Q13425-1A0A024R732
SNTB2	NR_172088.1 link	n.68C>T		non_coding_transcript_exon_variant	Exon 1 of 8
SNTB2	NR_172089.1 link	n.68C>T		non_coding_transcript_exon_variant	Exon 1 of 7
SNTB2	NR_172090.1 link	n.68C>T		non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SNTB2	ENST00000336278.9 link	c.65C>T	p.Ala22Val	missense_variant	Exon 1 of 7	1	NM_006750.4	ENSP00000338191.4	Q13425-1
SNTB2	ENST00000467311.5 link	n.65C>T		non_coding_transcript_exon_variant	Exon 1 of 6	1		ENSP00000436443.1	Q13425-2
UTP4	ENST00000567287.2 link	n.82+20046C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

GnomAD4 exome

AF:

0.00000154

AC:

AN:

1300638

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

642310

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000329

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000262

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

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

Jan 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.65C>T (p.A22V) alteration is located in exon 1 (coding exon 1) of the SNTB2 gene. This alteration results from a C to T substitution at nucleotide position 65, causing the alanine (A) at amino acid position 22 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

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.42

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.8

PrimateAI

Pathogenic

0.98

PROVEAN

Benign

-0.97

REVEL

Benign

0.21

Sift

Benign

0.041

Sift4G

Benign

0.19

Polyphen

0.99

Vest4

0.41

MutPred

0.67

Gain of sheet (P = 0.0266);

MVP

0.76

MPC

1.5

ClinPred

0.88

GERP RS

4.1

Varity_R

0.19

gMVP

0.77

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