NM_006750.4:c.416C>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006750.4(SNTB2):c.416C>T(p.Pro139Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000847 in 1,534,806 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 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

SNTB2
NM_006750.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.47

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.89

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.416C>T	p.Pro139Leu	missense	Exon 1 of 7	NP_006741.1	Q13425-1
SNTB2	NR_172088.1		n.419C>T		non_coding_transcript_exon	Exon 1 of 8
SNTB2	NR_172089.1		n.419C>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.416C>T	p.Pro139Leu	missense	Exon 1 of 7	ENSP00000338191.4	Q13425-1
SNTB2	ENST00000467311.5	TSL:1	n.416C>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000436443.1	Q13425-2
SNTB2	ENST00000958019.1		c.416C>T	p.Pro139Leu	missense	Exon 1 of 7	ENSP00000628078.1

Frequencies

GnomAD3 genomes

AF:

0.0000397

AC:

AN:

151120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000971

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:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000506

AC:

AN:

1383686

Hom.:

Cov.:

AF XY:

0.00000438

AC XY:

AN XY:

684914

show subpopulations

African (AFR)

AF:

0.0000347

AC:

AN:

28798

American (AMR)

AF:

0.00

AC:

AN:

32992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23974

East Asian (EAS)

AF:

0.00

AC:

AN:

32220

South Asian (SAS)

AF:

0.00

AC:

AN:

76994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48754

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5544

European-Non Finnish (NFE)

AF:

0.00000557

AC:

AN:

1077480

Other (OTH)

AF:

0.00

AC:

AN:

56930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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:

0.0000397

AC:

AN:

151120

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73800

show subpopulations

African (AFR)

AF:

0.0000971

AC:

AN:

41192

American (AMR)

AF:

0.00

AC:

AN:

15176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67652

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.00

Hom.:

Bravo

AF:

0.0000491

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

1.0

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.66

MetaRNN

Pathogenic

0.89

MetaSVM

Uncertain

-0.20

MutationAssessor

Pathogenic

3.0

PhyloP100

4.5

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-8.1

REVEL

Uncertain

0.37

Sift

Uncertain

0.016

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.62

MVP

0.71

MPC

2.6

ClinPred

1.0

GERP RS

4.1

PromoterAI

0.032

Neutral

(source)

Varity_R

0.89

gMVP

0.88

Mutation Taster

=8/92

disease causing

(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