NM_145263.4:c.314C>T

Variant names:

• chr4-52062224-C-T
• rs113402846
• NM_145263.4:c.314C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145263.4(SPATA18):​c.314C>T​(p.Thr105Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000244 in 1,516,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000042 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: SPATA18 NM_145263.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19819579).

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.314C>T	p.Thr105Met	missense	Exon 4 of 13	NP_660306.1	Q8TC71-1
	SPATA18	NM_001297608.2		c.314C>T	p.Thr105Met	missense	Exon 4 of 12	NP_001284537.1	Q8TC71-2
	SPATA18	NM_001346102.2		c.107+1327C>T		intron	N/A	NP_001333031.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA18	ENST00000295213.9	TSL:1 MANE Select	c.314C>T	p.Thr105Met	missense	Exon 4 of 13	ENSP00000295213.4	Q8TC71-1
	SPATA18	ENST00000419395.6	TSL:2	c.314C>T	p.Thr105Met	missense	Exon 4 of 12	ENSP00000415309.2	Q8TC71-2
	SPATA18	ENST00000851879.1		c.314C>T	p.Thr105Met	missense	Exon 4 of 12	ENSP00000521938.1

Frequencies

GnomAD3 genomes AF: 0.0000348 AC: 5 AN: 143774 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000779

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: 0.000119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000268 AC: 6 AN: 223724 AF XY: 0.00000824

Gnomad AFR exome AF: 0.000199

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000519

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 31 AN: 1372304 Hom.: 0 Cov.: 25 AF XY: 0.0000205 AC XY: 14 AN XY: 683036

African (AFR) AF: 0.000166 AC: 5 AN: 30174

American (AMR) AF: 0.00 AC: 0 AN: 37912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24298

East Asian (EAS) AF: 0.00 AC: 0 AN: 37894

South Asian (SAS) AF: 0.00 AC: 0 AN: 77028

European-Finnish (FIN) AF: 0.0000992 AC: 5 AN: 50428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5204

European-Non Finnish (NFE) AF: 0.0000124 AC: 13 AN: 1052574

Other (OTH) AF: 0.000141 AC: 8 AN: 56792

GnomAD4 genome AF: 0.0000417 AC: 6 AN: 143858 Hom.: 0 Cov.: 30 AF XY: 0.0000865 AC XY: 6 AN XY: 69346

African (AFR) AF: 0.000104 AC: 4 AN: 38624

American (AMR) AF: 0.00 AC: 0 AN: 14074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 4918

South Asian (SAS) AF: 0.00 AC: 0 AN: 4560

European-Finnish (FIN) AF: 0.000119 AC: 1 AN: 8370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66716

Other (OTH) AF: 0.00 AC: 0 AN: 2004

Alfa AF: 0.0000217 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

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	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.030
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.3
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.040
Sift	Benign	0.030	D
Sift4G	Uncertain	0.022	D
Polyphen		0.98	D
Vest4		0.48
MVP		0.16
MPC		0.68
ClinPred		0.18	T
GERP RS		4.2
Varity_R		0.047
gMVP		0.29
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs113402846; hg19: chr4-52928390; COSMIC: COSV54645840;