7-141743569-C-T

Variant names:

• chr7-141743569-C-T
• rs774947843
• NM_003143.3:c.94C>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1 PP3 BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98

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 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
SSBP1	NM_003143.3	c.94C>T	p.Arg32Cys	missense_variant	Exon 4 of 7	ENST00000265304.11	NP_003134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSBP1	ENST00000265304.11	c.94C>T	p.Arg32Cys	missense_variant	Exon 4 of 7	1	NM_003143.3	ENSP00000265304.6

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152114 Hom.: 0 Cov.: 33

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

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

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

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

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

Other links and lift over

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