5-81442696-T-C

Variant names:

• chr5-81442696-T-C
• rs1415677981
• NM_001256732.3:c.830A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001256732.3(SSBP2):​c.830A>G​(p.Tyr277Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000126 in 1,581,760 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SSBP2 NM_001256732.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSBP2	NM_001256732.3	c.830A>G	p.Tyr277Cys	missense_variant	Exon 13 of 17	ENST00000615665.5	NP_001243661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSBP2	ENST00000615665.5	c.830A>G	p.Tyr277Cys	missense_variant	Exon 13 of 17	5	NM_001256732.3	ENSP00000483921.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1429596 Hom.: 0 Cov.: 25 AF XY: 0.00000140 AC XY: 1 AN XY: 711974

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.14e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74344

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

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: 0.000224 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.806A>G (p.Y269C) alteration is located in exon 13 (coding exon 13) of the SSBP2 gene. This alteration results from a A to G substitution at nucleotide position 806, causing the tyrosine (Y) at amino acid position 269 to be replaced by a cysteine (C). 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	0.68
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D;T;.;.;T;T;.;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.78	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.0054	D
MutationAssessor	Pathogenic	3.0	M;.;.;.;.;.;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-7.8	D;.;D;D;D;D;D;D
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D;.;D;D;D;D;D;D
Sift4G	Uncertain	0.036	D;T;T;T;T;D;D;D
Polyphen		0.99	D;.;.;.;.;.;.;.
Vest4		0.86
MutPred		0.50		Loss of phosphorylation at Y269 (P = 0.0017);.;.;.;.;.;.;.;
MVP		0.31
MPC		2.2
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.90
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1415677981; hg19: chr5-80738515;