chr4-52060832-C-T

Variant names:

• chr4-52060832-C-T
• rs535954416
• NM_145263.4:c.244C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_145263.4(SPATA18):​c.244C>T​(p.Leu82Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA18 NM_145263.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.807
• Publications: 0 publications found

Genes affected

SPATA18 (HGNC:29579): (spermatogenesis associated 18) This gene encodes a p53-inducible protein that is able to induce lysosome-like organelles within mitochondria that eliminate oxidized mitochondrial proteins, thereby contributing to mitochondrial quality control. Dysregulation of mitochondrial quality control is associated with cancer and degenerative diseases. The encoded protein mediates accumulation of the lysosome-like mitochondrial organelles through interaction with B cell lymphoma 2 interacting protein 3 and B cell lymphoma 2 interacting protein 3 like at the outer mitochondrial membrane, which allows translocation of lysosomal proteins to the mitochondrial matrix from the cytosol. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=0.807 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145263.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA18	NM_145263.4	MANE Select	c.244C>T	p.Leu82Leu	synonymous	Exon 3 of 13	NP_660306.1	Q8TC71-1
	SPATA18	NM_001297608.2		c.244C>T	p.Leu82Leu	synonymous	Exon 3 of 12	NP_001284537.1	Q8TC71-2
	SPATA18	NM_001346102.2		c.42C>T	p.Gly14Gly	synonymous	Exon 3 of 11	NP_001333031.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA18	ENST00000295213.9	TSL:1 MANE Select	c.244C>T	p.Leu82Leu	synonymous	Exon 3 of 13	ENSP00000295213.4	Q8TC71-1
	SPATA18	ENST00000419395.6	TSL:2	c.244C>T	p.Leu82Leu	synonymous	Exon 3 of 12	ENSP00000415309.2	Q8TC71-2
	SPATA18	ENST00000851879.1		c.244C>T	p.Leu82Leu	synonymous	Exon 3 of 12	ENSP00000521938.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.6
DANN	Benign	0.59
PhyloP100		0.81

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: rs535954416; hg19: chr4-52926998; COSMIC: COSV54641839;