7-141743934-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_003143.3(SSBP1):c.259A>C(p.Ile87Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SSBP1 NM_003143.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56

Genes affected

SSBP1 (HGNC:11317): (single stranded DNA binding protein 1) SSBP1 is a housekeeping gene involved in mitochondrial biogenesis (Tiranti et al., 1995 [PubMed 7789991]). It is also a subunit of a single-stranded DNA (ssDNA)-binding complex involved in the maintenance of genome stability (Huang et al., 2009) [PubMed 19683501].[supplied by OMIM, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a domain SSB (size 111) in uniprot entity SSBP_HUMAN there are 7 pathogenic changes around while only 0 benign (100%) in NM_003143.3
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39372972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSBP1	NM_003143.3	c.259A>C	p.Ile87Leu	missense_variant	5/7	ENST00000265304.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSBP1	ENST00000265304.11	c.259A>C	p.Ile87Leu	missense_variant	5/7	1	NM_003143.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2023

The c.259A>C (p.I87L) alteration is located in exon 5 (coding exon 4) of the SSBP1 gene. This alteration results from a A to C substitution at nucleotide position 259, causing the isoleucine (I) at amino acid position 87 to be replaced by a leucine (L). 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	0.79
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
Cadd	Pathogenic	26
Dann	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T;T;T;T;T;T;T
Eigen	Benign	-0.025
Eigen_PC	Benign	0.041
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.39	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.7	L;L;L;.;L;.;L;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.9	N;.;N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0080	D;.;D;D;D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D;D;D;D;D
Polyphen		0.47	P;P;P;.;P;.;P;P
Vest4		0.50
MutPred		0.69		Gain of catalytic residue at I87 (P = 0.0558);Gain of catalytic residue at I87 (P = 0.0558);Gain of catalytic residue at I87 (P = 0.0558);Gain of catalytic residue at I87 (P = 0.0558);Gain of catalytic residue at I87 (P = 0.0558);Gain of catalytic residue at I87 (P = 0.0558);Gain of catalytic residue at I87 (P = 0.0558);Gain of catalytic residue at I87 (P = 0.0558);
MVP		0.47
MPC		1.0
ClinPred		0.80	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.90
gMVP		0.72

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: chr7-141443734;