Variant 10-79432751-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153367.4(ZCCHC24):c.254G>C(p.Ser85Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZCCHC24
NM_153367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

Variant links:

Genes affected

ZCCHC24 (HGNC:26911): (zinc finger CCHC-type containing 24) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZCCHC24 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2038734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC24	NM_153367.4 linkuse as main transcript	c.254G>C	p.Ser85Thr	missense_variant	2/4	ENST00000372336.4	NP_699198.2	Q8N2G6A0A024QZP0
ZCCHC24	XM_011539452.4 linkuse as main transcript	c.44G>C	p.Ser15Thr	missense_variant	2/4		XP_011537754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCCHC24	ENST00000372336.4 linkuse as main transcript	c.254G>C	p.Ser85Thr	missense_variant	2/4	1	NM_153367.4	ENSP00000361411.3		Q8N2G6
ZCCHC24	ENST00000372333.3 linkuse as main transcript	c.75G>C	p.Glu25Asp	missense_variant	2/4	2		ENSP00000361408.3		Q5W133

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243434

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132126

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455942

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724400

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

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

Sep 20, 2023

The c.254G>C (p.S85T) alteration is located in exon 2 (coding exon 2) of the ZCCHC24 gene. This alteration results from a G to C substitution at nucleotide position 254, causing the serine (S) at amino acid position 85 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

0.077

BayesDel_addAF

Benign

0.00015

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.18

Eigen_PC

Benign

0.027

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.39

M_CAP

Benign

0.014

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

PROVEAN

Benign

-2.0

REVEL

Benign

0.28

Polyphen

0.79

Vest4

0.37

MutPred

0.085

Gain of loop (P = 0.0435);

MVP

0.040

ClinPred

0.23

GERP RS

6.0

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