5-81751009-C-T

Variant names:

• chr5-81751009-C-T
• rs757708024
• NM_001256732.3:c.34G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256732.3(SSBP2):​c.34G>A​(p.Val12Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,064 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: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SSBP2 NM_001256732.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11406919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSBP2	NM_001256732.3	c.34G>A	p.Val12Ile	missense_variant	Exon 1 of 17	ENST00000615665.5	NP_001243661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSBP2	ENST00000615665.5	c.34G>A	p.Val12Ile	missense_variant	Exon 1 of 17	5	NM_001256732.3	ENSP00000483921.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447064 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718390

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.34G>A (p.V12I) alteration is located in exon 1 (coding exon 1) of the SSBP2 gene. This alteration results from a G to A substitution at nucleotide position 34, causing the valine (V) at amino acid position 12 to be replaced by an isoleucine (I). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;T;.;.;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.054
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.69	N;.;N;N;N;N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.73	N;.;N;N;N;N
REVEL	Benign	0.088
Sift	Uncertain	0.025	D;.;D;D;D;D
Sift4G	Benign	0.20	T;T;T;T;T;T
Polyphen		0.0020	B;.;.;.;.;.
Vest4		0.15
MutPred		0.085		Loss of MoRF binding (P = 0.1643);Loss of MoRF binding (P = 0.1643);Loss of MoRF binding (P = 0.1643);Loss of MoRF binding (P = 0.1643);Loss of MoRF binding (P = 0.1643);Loss of MoRF binding (P = 0.1643);
MVP		0.082
MPC		0.70
ClinPred		0.48	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.35
gMVP		0.39

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

Other links and lift over

dbSNP: rs757708024; hg19: chr5-81046828;