Variant 5-81437449-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001256732.3(SSBP2):c.962A>G(p.Asp321Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000436 in 1,605,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

SSBP2
NM_001256732.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22

Variant links:

Genes affected

SSBP2 (HGNC:15831): (single stranded DNA binding protein 2) This gene encodes a subunit of a protein complex that interacts with single-stranded DNA and is involved in the DNA damage response and maintenance of genome stability. The encoded protein may also play a role in telomere repair. A variant of this gene may be associated with survival in human glioblastoma patients. [provided by RefSeq, Sep 2016]

SSBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity SSBP2_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSBP2	NM_001256732.3 link	c.962A>G	p.Asp321Gly	missense_variant	15/17	ENST00000615665.5	NP_001243661.1	P81877A0A087X159

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSBP2	ENST00000615665.5 link	c.962A>G	p.Asp321Gly	missense_variant	15/17	5	NM_001256732.3	ENSP00000483921.1		A0A087X159

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000205

AC:

AN:

244420

Hom.:

AF XY:

0.0000303

AC XY:

AN XY:

132158

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000614

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000468

AC:

AN:

1453894

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

723064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000703

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:

0.0000577

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000624

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.938A>G (p.D313G) alteration is located in exon 15 (coding exon 15) of the SSBP2 gene. This alteration results from a A to G substitution at nucleotide position 938, causing the aspartic acid (D) at amino acid position 313 to be replaced by a glycine (G). 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

0.76

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

D;T;.;.;T;.;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D;D;D;D;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.72

D;D;D;D;D;D;D

MetaSVM

Benign

-0.46

MutationAssessor

Benign

1.6

L;.;.;.;.;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.2

D;.;D;D;D;D;D

REVEL

Uncertain

0.39

Sift

Benign

0.074

T;.;D;D;D;D;D

Sift4G

Benign

0.23

T;T;T;T;T;T;T

Polyphen

0.96

D;.;.;.;.;.;.

Vest4

0.81

MVP

0.53

MPC

2.1

ClinPred

0.80

GERP RS

5.5

Varity_R

0.38

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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