7-141750329-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1 PM2 PP5 BP4

The NM_003143.3(SSBP1):c.422G>A(p.Ser141Asn) variant causes a missense change. 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SSBP1 NM_003143.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.07

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 4 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
• PP5: Variant 7-141750329-G-A is Pathogenic according to our data. Variant chr7-141750329-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 977504.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.24407443).. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSBP1	NM_003143.3	c.422G>A	p.Ser141Asn	missense_variant	7/7	ENST00000265304.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSBP1	ENST00000265304.11	c.422G>A	p.Ser141Asn	missense_variant	7/7	1	NM_003143.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Optic atrophy 13 with retinal and foveal abnormalities Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 03, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.099	T;T;T;T;T;T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.8	M;M;M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.10	N;.;N;N;N;N
REVEL	Benign	0.084
Sift	Benign	0.20	T;.;T;T;T;T
Sift4G	Benign	0.28	T;T;T;T;T;T
Polyphen		0.0010	B;B;B;B;B;B
Vest4		0.38
MutPred		0.37		Loss of ubiquitination at K145 (P = 0.1441);Loss of ubiquitination at K145 (P = 0.1441);Loss of ubiquitination at K145 (P = 0.1441);Loss of ubiquitination at K145 (P = 0.1441);Loss of ubiquitination at K145 (P = 0.1441);Loss of ubiquitination at K145 (P = 0.1441);
MVP		0.60
MPC		0.52
ClinPred		0.87	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs1799915649; hg19: chr7-141450129;