chr16-69187723-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006750.4(SNTB2):c.557C>T(p.Ala186Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000497 in 1,227,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

SNTB2
NM_006750.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hereditary North American Indian childhood cirrhosis
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet
cirrhosis, familial
Inheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics

UTP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3337431).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006750.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNTB2	NM_006750.4	MANE Select	c.557C>T	p.Ala186Val	missense	Exon 1 of 7	NP_006741.1	Q13425-1
SNTB2	NR_172088.1		n.560C>T		non_coding_transcript_exon	Exon 1 of 8
SNTB2	NR_172089.1		n.560C>T		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNTB2	ENST00000336278.9	TSL:1 MANE Select	c.557C>T	p.Ala186Val	missense	Exon 1 of 7	ENSP00000338191.4	Q13425-1
SNTB2	ENST00000467311.5	TSL:1	n.557C>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000436443.1	Q13425-2
SNTB2	ENST00000958019.1		c.557C>T	p.Ala186Val	missense	Exon 1 of 7	ENSP00000628078.1

Frequencies

GnomAD3 genomes

AF:

0.0000478

AC:

AN:

125434

Hom.:

Cov.:

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:

0.0000993

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000403

AC:

AN:

124214

AF XY:

0.0000564

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000917

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000499

AC:

AN:

1101914

Hom.:

Cov.:

AF XY:

0.0000478

AC XY:

AN XY:

543718

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20746

American (AMR)

AF:

0.00

AC:

AN:

26760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14998

East Asian (EAS)

AF:

0.00

AC:

AN:

9248

South Asian (SAS)

AF:

0.00

AC:

AN:

73528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3394

European-Non Finnish (NFE)

AF:

0.0000591

AC:

AN:

897414

Other (OTH)

AF:

0.0000500

AC:

AN:

40004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000478

AC:

AN:

125434

Hom.:

Cov.:

AF XY:

0.0000668

AC XY:

AN XY:

59836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33666

American (AMR)

AF:

0.00

AC:

AN:

11898

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3172

East Asian (EAS)

AF:

0.00

AC:

AN:

3644

South Asian (SAS)

AF:

0.00

AC:

AN:

3526

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.0000993

AC:

AN:

60412

Other (OTH)

AF:

0.00

AC:

AN:

1726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

ExAC

AF:

0.00000880

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.085

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.7

PhyloP100

5.3

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.1

REVEL

Benign

0.15

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0090

Polyphen

0.87

Vest4

0.46

MutPred

0.59

Gain of MoRF binding (P = 0.1043)

MVP

0.60

MPC

0.36

ClinPred

0.72

GERP RS

3.4

PromoterAI

0.012

Neutral

(source)

Varity_R

0.67

gMVP

0.74

Mutation Taster

=54/46

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over