Variant 4-25362279-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024936.3(ZCCHC4):c.1187T>A(p.Leu396His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 1,606,556 control chromosomes in the GnomAD database, including 638,947 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.91 ( 62801 hom., cov: 32)

Exomes 𝑓: 0.89 ( 576146 hom. )

Consequence

ZCCHC4
NM_024936.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.87

Variant links:

Genes affected

ZCCHC4 (HGNC:22917): (zinc finger CCHC-type containing 4) Enables S-adenosyl-L-methionine binding activity; rRNA (adenine-N6-)-methyltransferase activity; and zinc ion binding activity. Involved in positive regulation of translation and rRNA methylation. Located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ZCCHC4 links:

ZCCHC4 (HGNC:):

ZCCHC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.5607344E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC4	NM_024936.3 linkuse as main transcript	c.1187T>A	p.Leu396His	missense_variant	10/13	ENST00000302874.9	NP_079212.2	Q9H5U6-1
ZCCHC4	XM_011513835.3 linkuse as main transcript	c.1232T>A	p.Leu411His	missense_variant	11/14		XP_011512137.1
ZCCHC4	XM_017008129.3 linkuse as main transcript	c.935T>A	p.Leu312His	missense_variant	8/11		XP_016863618.1
ZCCHC4	XR_925324.4 linkuse as main transcript	n.1268T>A		non_coding_transcript_exon_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCCHC4	ENST00000302874.9 linkuse as main transcript	c.1187T>A	p.Leu396His	missense_variant	10/13	1	NM_024936.3	ENSP00000303468.4		Q9H5U6-1

Frequencies

GnomAD3 genomes

AF:

0.906

AC:

137922

AN:

152166

Hom.:

62739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.976

Gnomad AMI

AF:

0.882

Gnomad AMR

AF:

0.869

Gnomad ASJ

AF:

0.852

Gnomad EAS

AF:

0.763

Gnomad SAS

AF:

0.828

Gnomad FIN

AF:

0.920

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.890

Gnomad OTH

AF:

0.903

GnomAD3 exomes

AF:

0.873

AC:

216607

AN:

248096

Hom.:

94927

AF XY:

0.871

AC XY:

117294

AN XY:

134660

show subpopulations

Gnomad AFR exome

AF:

0.980

Gnomad AMR exome

AF:

0.838

Gnomad ASJ exome

AF:

0.862

Gnomad EAS exome

AF:

0.770

Gnomad SAS exome

AF:

0.832

Gnomad FIN exome

AF:

0.921

Gnomad NFE exome

AF:

0.888

Gnomad OTH exome

AF:

0.877

GnomAD4 exome

AF:

0.889

AC:

1293415

AN:

1454272

Hom.:

576146

Cov.:

AF XY:

0.887

AC XY:

641505

AN XY:

723400

show subpopulations

Gnomad4 AFR exome

AF:

0.983

Gnomad4 AMR exome

AF:

0.841

Gnomad4 ASJ exome

AF:

0.858

Gnomad4 EAS exome

AF:

0.805

Gnomad4 SAS exome

AF:

0.829

Gnomad4 FIN exome

AF:

0.918

Gnomad4 NFE exome

AF:

0.896

Gnomad4 OTH exome

AF:

0.885

GnomAD4 genome

AF:

0.906

AC:

138043

AN:

152284

Hom.:

62801

Cov.:

AF XY:

0.906

AC XY:

67454

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.976

Gnomad4 AMR

AF:

0.869

Gnomad4 ASJ

AF:

0.852

Gnomad4 EAS

AF:

0.763

Gnomad4 SAS

AF:

0.828

Gnomad4 FIN

AF:

0.920

Gnomad4 NFE

AF:

0.890

Gnomad4 OTH

AF:

0.905

Alfa

AF:

0.889

Hom.:

45422

Bravo

AF:

0.908

TwinsUK

AF:

0.909

AC:

3371

ALSPAC

AF:

0.905

AC:

3486

ESP6500AA

AF:

0.976

AC:

3576

ESP6500EA

AF:

0.894

AC:

7299

ExAC

AF:

0.874

AC:

105606

Asia WGS

AF:

0.813

AC:

2828

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0033

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.037

MetaRNN

Benign

0.0000026

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.1

PrimateAI

Benign

0.46

PROVEAN

Benign

0.64

REVEL

Benign

0.074

Sift

Benign

0.16

Sift4G

Benign

0.25

Polyphen

0.0

Vest4

0.072

MPC

0.10

ClinPred

0.0092

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.16

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over