7-141743641-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_003143.3(SSBP1):c.166A>G(p.Ile56Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SSBP1 NM_003143.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.28

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 3 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
• BP4: Computational evidence support a benign effect (MetaRNN=0.40519676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSBP1	NM_003143.3	c.166A>G	p.Ile56Val	missense_variant	4/7	ENST00000265304.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSBP1	ENST00000265304.11	c.166A>G	p.Ile56Val	missense_variant	4/7	1	NM_003143.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.078	T;T;T;T;T;T;T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.41	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.86	L;L;L;.;L;.;L;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.060	N;.;N;N;N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.46	T;.;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T
Polyphen		0.79	P;P;P;.;P;.;P;P
Vest4		0.63
MutPred		0.47		Gain of catalytic residue at I56 (P = 0.0262);Gain of catalytic residue at I56 (P = 0.0262);Gain of catalytic residue at I56 (P = 0.0262);Gain of catalytic residue at I56 (P = 0.0262);Gain of catalytic residue at I56 (P = 0.0262);Gain of catalytic residue at I56 (P = 0.0262);Gain of catalytic residue at I56 (P = 0.0262);Gain of catalytic residue at I56 (P = 0.0262);
MVP		0.66
MPC		0.73
ClinPred		0.68	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.41

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: rs1799655635; hg19: chr7-141443441;