chr4-52060426-C-T

Variant names:

• chr4-52060426-C-T
• rs1039849838
• NM_145263.4:c.95C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001346102.2(SPATA18):​c.-108C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000112 in 1,613,668 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: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: SPATA18 NM_001346102.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.14
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40539402).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346102.2. 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.95C>T	p.Thr32Met	missense	Exon 2 of 13	NP_660306.1	Q8TC71-1
	SPATA18	NM_001346102.2		c.-108C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	NP_001333031.1
	SPATA18	NM_001297608.2		c.95C>T	p.Thr32Met	missense	Exon 2 of 12	NP_001284537.1	Q8TC71-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA18	ENST00000295213.9	TSL:1 MANE Select	c.95C>T	p.Thr32Met	missense	Exon 2 of 13	ENSP00000295213.4	Q8TC71-1
	SPATA18	ENST00000419395.6	TSL:2	c.95C>T	p.Thr32Met	missense	Exon 2 of 12	ENSP00000415309.2	Q8TC71-2
	SPATA18	ENST00000851879.1		c.95C>T	p.Thr32Met	missense	Exon 2 of 12	ENSP00000521938.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251186 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461492 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727056

African (AFR) AF: 0.0000299 AC: 1 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111780

Other (OTH) AF: 0.000132 AC: 8 AN: 60384

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74356

African (AFR) AF: 0.0000483 AC: 2 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.1
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.22		Loss of helix (P = 0.2271)
MVP		0.31
MPC		0.54
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.14
gMVP		0.54
Mutation Taster		=70/30	polymorphism

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: rs1039849838; hg19: chr4-52926592; COSMIC: COSV54641785;