chr5-81442689-T-G

Variant names:

• chr5-81442689-T-G
• rs1486296096
• NM_001256732.3:c.837A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001256732.3(SSBP2):​c.837A>C​(p.Leu279Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,582,878 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: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: SSBP2 NM_001256732.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27741593).

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.837A>C	p.Leu279Phe	missense	Exon 13 of 17	NP_001243661.1	A0A087X159
	SSBP2	NM_001394350.1		c.873A>C	p.Leu291Phe	missense	Exon 14 of 18	NP_001381279.1
	SSBP2	NM_001400340.1		c.837A>C	p.Leu279Phe	missense	Exon 13 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.837A>C	p.Leu279Phe	missense	Exon 13 of 17	ENSP00000483921.1	A0A087X159
	SSBP2	ENST00000320672.9	TSL:1	c.813A>C	p.Leu271Phe	missense	Exon 13 of 17	ENSP00000322977.4	P81877-1
	SSBP2	ENST00000514493.5	TSL:1	c.723A>C	p.Leu241Phe	missense	Exon 12 of 16	ENSP00000426183.1	P81877-4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152138 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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000861 AC: 2 AN: 232240 AF XY: 0.00000794

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000184

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000979 AC: 14 AN: 1430740 Hom.: 0 Cov.: 25 AF XY: 0.00000702 AC XY: 5 AN XY: 712392

African (AFR) AF: 0.00 AC: 0 AN: 32038

American (AMR) AF: 0.00 AC: 0 AN: 39112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25476

East Asian (EAS) AF: 0.00 AC: 0 AN: 38864

South Asian (SAS) AF: 0.00 AC: 0 AN: 81584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.0000119 AC: 13 AN: 1095618

Other (OTH) AF: 0.0000169 AC: 1 AN: 59132

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74322

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.074
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.59	T
Polyphen		0.91	P
Vest4		0.43
MutPred		0.40		Loss of sheet (P = 0.1158)
MVP		0.082
MPC		1.5
ClinPred		0.71	D
GERP RS		5.1
Varity_R		0.33
gMVP		0.64
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1486296096; hg19: chr5-80738508;