Variant chr7-141743588-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_ModeratePP5_Moderate

The ENST00000265304.11(SSBP1):c.113G>A(p.Arg38Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SSBP1
ENST00000265304.11 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 8.88

Variant links:

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]

SSBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 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 ENST00000265304.11

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.861

PP5

Variant 7-141743588-G-A is Pathogenic according to our data. Variant chr7-141743588-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 977502.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSBP1	NM_003143.3 linkuse as main transcript	c.113G>A	p.Arg38Gln	missense_variant	4/7	ENST00000265304.11	NP_003134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSBP1	ENST00000265304.11 linkuse as main transcript	c.113G>A	p.Arg38Gln	missense_variant	4/7	1	NM_003143.3	ENSP00000265304	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Optic atrophy 13 with retinal and foveal abnormalities

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 03, 2020

- -

Cone-rod dystrophy

Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel

Jul 24, 2023

Clinical significance based on ACMG v2.0 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.54

D;D;D;T;D;T;D;D

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

.;D;.;D;.;.;.;.

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.86

D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.25

MutationAssessor

Pathogenic

3.4

M;M;M;.;M;.;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.2

D;.;D;D;D;D;D;D

REVEL

Uncertain

0.51

Sift

Uncertain

0.0030

D;.;D;D;D;D;D;D

Sift4G

Uncertain

0.016

D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;.;D;.;D;D

Vest4

0.85

MutPred

0.66

Loss of MoRF binding (P = 0.0164);Loss of MoRF binding (P = 0.0164);Loss of MoRF binding (P = 0.0164);Loss of MoRF binding (P = 0.0164);Loss of MoRF binding (P = 0.0164);Loss of MoRF binding (P = 0.0164);Loss of MoRF binding (P = 0.0164);Loss of MoRF binding (P = 0.0164);

MVP

0.73

MPC

1.1

ClinPred

0.97

GERP RS

5.7

Varity_R

0.91

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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