5-81751009-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 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 0 ACMG points.

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

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.34G>A	p.Val12Ile	missense	Exon 1 of 17	NP_001243661.1	A0A087X159
	SSBP2	NM_001394350.1		c.34G>A	p.Val12Ile	missense	Exon 1 of 18	NP_001381279.1
	SSBP2	NM_001400340.1		c.34G>A	p.Val12Ile	missense	Exon 1 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.34G>A	p.Val12Ile	missense	Exon 1 of 17	ENSP00000483921.1	A0A087X159
	SSBP2	ENST00000320672.9	TSL:1	c.34G>A	p.Val12Ile	missense	Exon 1 of 17	ENSP00000322977.4	P81877-1
	SSBP2	ENST00000514493.5	TSL:1	c.34G>A	p.Val12Ile	missense	Exon 1 of 16	ENSP00000426183.1	P81877-4

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

African (AFR) AF: 0.00 AC: 0 AN: 33194

American (AMR) AF: 0.00 AC: 0 AN: 42942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25820

East Asian (EAS) AF: 0.00 AC: 0 AN: 38820

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105154

Other (OTH) AF: 0.00 AC: 0 AN: 59712

GnomAD4 genome Cov.: 31

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	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
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.054
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.088
Sift	Uncertain	0.025	D
Sift4G	Benign	0.20	T
Polyphen		0.0020	B
Vest4		0.15
MutPred		0.085		Loss of MoRF binding (P = 0.1643)
MVP		0.082
MPC		0.70
ClinPred		0.48	T
GERP RS		3.7
PromoterAI		0.069	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.35
gMVP		0.39
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs757708024; hg19: chr5-81046828;