Variant 10-79432707-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153367.4(ZCCHC24):c.298A>G(p.Asn100Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000379 in 1,609,478 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ZCCHC24
NM_153367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZCCHC24	NM_153367.4 linkuse as main transcript	c.298A>G	p.Asn100Asp	missense_variant	2/4	ENST00000372336.4
ZCCHC24	XM_011539452.4 linkuse as main transcript	c.88A>G	p.Asn30Asp	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZCCHC24	ENST00000372336.4 linkuse as main transcript	c.298A>G	p.Asn100Asp	missense_variant	2/4	1	NM_153367.4	P1
ZCCHC24	ENST00000372333.3 linkuse as main transcript	c.119A>G	p.Gln40Arg	missense_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000488

AC:

AN:

246086

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

133284

show subpopulations

Gnomad AFR exome

AF:

0.000748

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1457222

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

725042

show subpopulations

Gnomad4 AFR exome

AF:

0.000664

Gnomad4 AMR exome

AF:

0.0000924

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:

0.0000499

GnomAD4 genome

AF:

0.000210

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.000196

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:

0.0000722

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

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

Apr 25, 2022

The c.298A>G (p.N100D) alteration is located in exon 2 (coding exon 2) of the ZCCHC24 gene. This alteration results from a A to G substitution at nucleotide position 298, causing the asparagine (N) at amino acid position 100 to be replaced by an aspartic acid (D). 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

0.24

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.7

REVEL

Benign

0.24

Sift

Benign

0.24

Sift4G

Benign

0.39

Polyphen

1.0

Vest4

0.87

MVP

0.25

MPC

1.0

ClinPred

0.13

GERP RS

6.0

Varity_R

0.33

gMVP

0.67

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