NM_003143.3:c.404-1415T>C

Variant names:

• chr7-141748896-T-C
• rs10485836
• NM_003143.3:c.404-1415T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003143.3(SSBP1):​c.404-1415T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 152,340 control chromosomes in the GnomAD database, including 227 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.036 (227 hom., cov: 32)
• Consequence: SSBP1 NM_003143.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• optic atrophy 13 with retinal and foveal abnormalities

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics
• Leigh syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003143.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSBP1	NM_003143.3	MANE Select	c.404-1415T>C		intron	N/A	NP_003134.1
	SSBP1	NM_001256510.1		c.404-1415T>C		intron	N/A	NP_001243439.1
	SSBP1	NM_001256511.1		c.404-1415T>C		intron	N/A	NP_001243440.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSBP1	ENST00000265304.11	TSL:1 MANE Select	c.404-1415T>C		intron	N/A	ENSP00000265304.6
	SSBP1	ENST00000481508.1	TSL:1	c.404-1415T>C		intron	N/A	ENSP00000419665.1
	SSBP1	ENST00000498107.5	TSL:1	c.404-1415T>C		intron	N/A	ENSP00000419541.1

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5430 AN: 152222 Hom.: 221 Cov.: 32

Gnomad AFR AF: 0.0795

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0324

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0645

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00416

Gnomad OTH AF: 0.0244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0358 AC: 5457 AN: 152340 Hom.: 227 Cov.: 32 AF XY: 0.0385 AC XY: 2867 AN XY: 74496

African (AFR) AF: 0.0796 AC: 3311 AN: 41576

American (AMR) AF: 0.0331 AC: 506 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.0644 AC: 334 AN: 5184

South Asian (SAS) AF: 0.153 AC: 738 AN: 4826

European-Finnish (FIN) AF: 0.0207 AC: 220 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00416 AC: 283 AN: 68034

Other (OTH) AF: 0.0237 AC: 50 AN: 2114

Alfa AF: 0.0115 Hom.: 35

Bravo AF: 0.0370

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.63
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10485836; hg19: chr7-141448696;