7-141743569-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PP3BS2

The NM_003143.3(SSBP1):​c.94C>T​(p.Arg32Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,918 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R32H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SSBP1
NM_003143.3 missense

Scores

5
12
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 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
PP3
MetaRNN computational evidence supports a deleterious effect, 0.821
BS2
High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSBP1NM_003143.3 linkc.94C>T p.Arg32Cys missense_variant Exon 4 of 7 ENST00000265304.11 NP_003134.1 Q04837A4D1U3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSBP1ENST00000265304.11 linkc.94C>T p.Arg32Cys missense_variant Exon 4 of 7 1 NM_003143.3 ENSP00000265304.6 Q04837

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152114
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251320
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1461804
Hom.:
0
Cov.:
31
AF XY:
0.0000165
AC XY:
12
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.0000162
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152114
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000959
Hom.:
0
Bravo
AF:
0.00000756
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jan 18, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.94C>T (p.R32C) alteration is located in exon 4 (coding exon 3) of the SSBP1 gene. This alteration results from a C to T substitution at nucleotide position 94, causing the arginine (R) at amino acid position 32 to be replaced by a cysteine (C). 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
Uncertain
0.35
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.43
T;T;T;T;T;T;T;T
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.90
.;D;.;D;.;.;.;.
M_CAP
Benign
0.021
T
MetaRNN
Pathogenic
0.82
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.0
D
MutationAssessor
Pathogenic
3.2
M;M;M;.;M;.;M;M
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-3.8
D;.;D;D;D;D;D;D
REVEL
Uncertain
0.46
Sift
Uncertain
0.0060
D;.;D;D;D;D;D;D
Sift4G
Uncertain
0.0060
D;D;D;D;D;D;D;D
Polyphen
1.0
D;D;D;.;D;.;D;D
Vest4
0.79
MutPred
0.76
Loss of MoRF binding (P = 0.0093);Loss of MoRF binding (P = 0.0093);Loss of MoRF binding (P = 0.0093);Loss of MoRF binding (P = 0.0093);Loss of MoRF binding (P = 0.0093);Loss of MoRF binding (P = 0.0093);Loss of MoRF binding (P = 0.0093);Loss of MoRF binding (P = 0.0093);
MVP
0.66
MPC
0.87
ClinPred
0.93
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.68
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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.

Other links and lift over

dbSNP: rs774947843; hg19: chr7-141443369; COSMIC: COSV54681020; COSMIC: COSV54681020; API