X-104115078-A-G

Position:

• chrX-104115078-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_001143978.3(ZCCHC18):​c.967A>G​(p.Thr323Ala) variant causes a missense 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. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZCCHC18 NM_001143978.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.583

Genes affected

ZCCHC18 (HGNC:32459): (zinc finger CCHC-type containing 18) Predicted to enable metal ion binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SLC25A53 (HGNC:31894): (solute carrier family 25 member 53) Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045635313).
• BP6: Variant X-104115078-A-G is Benign according to our data. Variant chrX-104115078-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1206047.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-104115078-A-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC18	NM_001143978.3	c.967A>G	p.Thr323Ala	missense_variant	3/3	ENST00000650639.1	NP_001137450.1
SLC25A53	NM_001012755.5	c.-31-9790T>C		intron_variant		ENST00000594199.3	NP_001012773.2
ZCCHC18	XM_011531012.4	c.967A>G	p.Thr323Ala	missense_variant	3/3		XP_011529314.1
ZCCHC18	NR_026694.3	n.672-174A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCCHC18	ENST00000650639.1	c.967A>G	p.Thr323Ala	missense_variant	3/3		NM_001143978.3	ENSP00000498828	P1
SLC25A53	ENST00000594199.3	c.-31-9790T>C		intron_variant		1	NM_001012755.5	ENSP00000468980	P1
ZCCHC18	ENST00000537356.3	c.967A>G	p.Thr323Ala	missense_variant	2/2	5		ENSP00000473824	P1
ZCCHC18	ENST00000422784.5	n.651-174A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.77
DEOGEN2	Benign	0.0029	T;T
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.00072	T
MetaRNN	Benign	0.046	T;T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.022	B;B
Vest4		0.086
MVP		0.12
MPC		0.18
GERP RS		1.0
Varity_R		0.056
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-103359769;