chr5-81448794-T-A

Variant names:

• chr5-81448794-T-A
• rs193920757
• NM_001256732.3:c.743A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001256732.3(SSBP2):​c.743A>T​(p.Tyr248Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SSBP2 NM_001256732.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.17
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256732.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSBP2	NM_001256732.3	MANE Select	c.743A>T	p.Tyr248Phe	missense	Exon 11 of 17	NP_001243661.1	A0A087X159
	SSBP2	NM_001394350.1		c.719A>T	p.Tyr240Phe	missense	Exon 11 of 18	NP_001381279.1
	SSBP2	NM_001400340.1		c.743A>T	p.Tyr248Phe	missense	Exon 11 of 18	NP_001387269.1	A0A087X159

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSBP2	ENST00000615665.5	TSL:5 MANE Select	c.743A>T	p.Tyr248Phe	missense	Exon 11 of 17	ENSP00000483921.1	A0A087X159
	SSBP2	ENST00000320672.9	TSL:1	c.719A>T	p.Tyr240Phe	missense	Exon 11 of 17	ENSP00000322977.4	P81877-1
	SSBP2	ENST00000514493.5	TSL:1	c.629A>T	p.Tyr210Phe	missense	Exon 10 of 16	ENSP00000426183.1	P81877-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.2
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.40	T
Polyphen		0.84	P
Vest4		0.72
MutPred		0.54		Loss of phosphorylation at Y240 (P = 0.0017)
MVP		0.33
MPC		1.3
ClinPred		0.97	D
GERP RS		6.0
Varity_R		0.57
gMVP		0.68
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs193920757; hg19: chr5-80744613; COSMIC: COSV57805339; COSMIC: COSV57805339;