Variant X-104114119-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000594199.3(SLC25A53):c.-31-8831C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,209,839 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., 16 hem., cov: 22)

Exomes 𝑓: 0.000059 ( 0 hom. 13 hem. )

Consequence

SLC25A53
ENST00000594199.3 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

Variant links:

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]

ZCCHC18 links:

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]

SLC25A53 links:

ZCCHC18 (HGNC:):

ZCCHC18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018903643).

BS2

High Hemizygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC18	NM_001143978.3 linkuse as main transcript	c.8G>C	p.Ser3Thr	missense_variant	3/3	ENST00000650639.1	NP_001137450.1	P0CG32
SLC25A53	NM_001012755.5 linkuse as main transcript	c.-31-8831C>G		intron_variant		ENST00000594199.3	NP_001012773.2	Q5H9E4
ZCCHC18	XM_011531012.4 linkuse as main transcript	c.8G>C	p.Ser3Thr	missense_variant	3/3		XP_011529314.1	P0CG32
ZCCHC18	NR_026694.3 linkuse as main transcript	n.671+546G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZCCHC18	ENST00000650639.1 linkuse as main transcript	c.8G>C	p.Ser3Thr	missense_variant	3/3		NM_001143978.3	ENSP00000498828.1	P0CG32
SLC25A53	ENST00000594199.3 linkuse as main transcript	c.-31-8831C>G		intron_variant		1	NM_001012755.5	ENSP00000468980.1	Q5H9E4
ZCCHC18	ENST00000537356.3 linkuse as main transcript	c.8G>C	p.Ser3Thr	missense_variant	2/2	5		ENSP00000473824.1	P0CG32
ZCCHC18	ENST00000422784.5 linkuse as main transcript	n.650+546G>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

111975

Hom.:

Cov.:

AF XY:

0.000469

AC XY:

AN XY:

34137

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000378

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

GnomAD3 exomes

AF:

0.000148

AC:

AN:

181965

Hom.:

AF XY:

0.0000749

AC XY:

AN XY:

66777

show subpopulations

Gnomad AFR exome

AF:

0.00194

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000592

AC:

AN:

1097809

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

363173

show subpopulations

Gnomad4 AFR exome

AF:

0.00224

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.000571

AC:

AN:

112030

Hom.:

Cov.:

AF XY:

0.000468

AC XY:

AN XY:

34202

show subpopulations

Gnomad4 AFR

AF:

0.00194

Gnomad4 AMR

AF:

0.000378

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000498

Hom.:

Bravo

AF:

0.000665

ExAC

AF:

0.000124

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 04, 2024

The c.8G>C (p.S3T) alteration is located in exon 3 (coding exon 1) of the ZCCHC18 gene. This alteration results from a G to C substitution at nucleotide position 8, causing the serine (S) at amino acid position 3 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.023

T;T

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.18

.;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.019

T;T

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.11

MVP

0.24

MPC

0.52

GERP RS

2.7

Varity_R

0.058

gMVP

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over