5-81650311-G-A

Variant names:

• chr5-81650311-G-A
• NM_001256732.3:c.91C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001256732.3(SSBP2):​c.91C>T​(p.Leu31Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,438,410 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: 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: 4.14

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3124944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSBP2	NM_001256732.3	c.91C>T	p.Leu31Phe	missense_variant	Exon 2 of 17	ENST00000615665.5	NP_001243661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSBP2	ENST00000615665.5	c.91C>T	p.Leu31Phe	missense_variant	Exon 2 of 17	5	NM_001256732.3	ENSP00000483921.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438410 Hom.: 0 Cov.: 28 AF XY: 0.00000140 AC XY: 1 AN XY: 714948

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: 9.08e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 21, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.91C>T (p.L31F) alteration is located in exon 2 (coding exon 2) of the SSBP2 gene. This alteration results from a C to T substitution at nucleotide position 91, causing the leucine (L) at amino acid position 31 to be replaced by a phenylalanine (F). 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	1.0
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.56	D;T;.;.;.;.;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.31	T;T;T;T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.5	M;.;M;M;M;M;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.9	D;.;D;D;D;D;D
REVEL	Benign	0.17
Sift	Benign	0.059	T;.;D;D;D;D;D
Sift4G	Benign	0.091	T;T;T;T;T;T;.
Polyphen		0.60	P;.;.;.;.;.;.
Vest4		0.82
MutPred		0.30		Loss of stability (P = 0.0506);Loss of stability (P = 0.0506);Loss of stability (P = 0.0506);Loss of stability (P = 0.0506);Loss of stability (P = 0.0506);Loss of stability (P = 0.0506);.;
MVP		0.44
MPC		2.0
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.49
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-80946130;