7-141742205-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_003143.3(SSBP1):c.61A>T(p.Thr21Ser) 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. 15/20 in silico tools predict 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: 0.525

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 0 ACMG points.

• PM1: In a chain Single-stranded DNA-binding protein, mitochondrial (size 131) 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=0.044994205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSBP1	NM_003143.3	c.61A>T	p.Thr21Ser	missense_variant	3/7	ENST00000265304.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSBP1	ENST00000265304.11	c.61A>T	p.Thr21Ser	missense_variant	3/7	1	NM_003143.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

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

Oct 27, 2023

The c.61A>T (p.T21S) alteration is located in exon 3 (coding exon 2) of the SSBP1 gene. This alteration results from a A to T substitution at nucleotide position 61, causing the threonine (T) at amino acid position 21 to be replaced by a serine (S). 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	Benign	0.075
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	0.34
Dann	Benign	0.65
DEOGEN2	Benign	0.073	T;T;T;T;T;T;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.17	N
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.045	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N;N;N;.;N;.;N;.;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.31	N;.;N;N;N;N;N;N;N
REVEL	Benign	0.031
Sift	Benign	0.76	T;.;T;T;T;T;T;.;T
Sift4G	Benign	0.73	T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;.;B;.;B;.;B
Vest4		0.20
MutPred		0.13		Gain of disorder (P = 0.069);Gain of disorder (P = 0.069);Gain of disorder (P = 0.069);Gain of disorder (P = 0.069);Gain of disorder (P = 0.069);Gain of disorder (P = 0.069);Gain of disorder (P = 0.069);Gain of disorder (P = 0.069);Gain of disorder (P = 0.069);
MVP		0.15
MPC		0.50
ClinPred		0.066	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.4
Varity_R		0.075
gMVP		0.19

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: chr7-141442005;