Genetic Variant NM_006750.4:c.302G>T (chr16-69187468-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006750.4(SNTB2):c.302G>T(p.Arg101Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R101Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SNTB2
NM_006750.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.278

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17076287).

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.302G>T	p.Arg101Leu	missense	Exon 1 of 7	NP_006741.1	Q13425-1
SNTB2	NR_172088.1		n.305G>T		non_coding_transcript_exon	Exon 1 of 8
SNTB2	NR_172089.1		n.305G>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.302G>T	p.Arg101Leu	missense	Exon 1 of 7	ENSP00000338191.4	Q13425-1
SNTB2	ENST00000467311.5	TSL:1	n.302G>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000436443.1	Q13425-2
SNTB2	ENST00000958019.1		c.302G>T	p.Arg101Leu	missense	Exon 1 of 7	ENSP00000628078.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1051954

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

496654

African (AFR)

AF:

0.00

AC:

AN:

21600

American (AMR)

AF:

0.00

AC:

AN:

7236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12660

East Asian (EAS)

AF:

0.00

AC:

AN:

23774

South Asian (SAS)

AF:

0.00

AC:

AN:

19224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2844

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

897506

Other (OTH)

AF:

0.00

AC:

AN:

40964

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.29

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.34

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

0.28

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.95

REVEL

Benign

0.13

Sift

Benign

0.28

Sift4G

Benign

0.27

Polyphen

0.14

Vest4

0.17

MutPred

0.36

Loss of solvent accessibility (P = 3e-04)

MVP

0.31

MPC

1.8

ClinPred

0.18

GERP RS

4.0

PromoterAI

0.095

Neutral

(source)

Varity_R

0.17

gMVP

0.43

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over