Variant rs3748400 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015144.3(ZCCHC14):c.2488G>A(p.Val830Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 1,613,764 control chromosomes in the GnomAD database, including 427,060 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 29049 hom., cov: 32)

Exomes 𝑓: 0.73 ( 398011 hom. )

Consequence

ZCCHC14
NM_015144.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

Variant links:

Genes affected

ZCCHC14 (HGNC:24134): (zinc finger CCHC-type containing 14) Predicted to enable nucleic acid binding activity; phosphatidylinositol binding activity; and zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZCCHC14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.772881E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZCCHC14	NM_015144.3 linkuse as main transcript	c.2488G>A	p.Val830Met	missense_variant	12/13	ENST00000671377.2	NP_055959.2
ZCCHC14	XM_005255858.4 linkuse as main transcript	c.2488G>A	p.Val830Met	missense_variant	12/12		XP_005255915.3
ZCCHC14	XM_017023082.3 linkuse as main transcript	c.1969G>A	p.Val657Met	missense_variant	12/12		XP_016878571.1
ZCCHC14	XR_243401.4 linkuse as main transcript	n.3274G>A		non_coding_transcript_exon_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCCHC14	ENST00000671377.2 linkuse as main transcript	c.2488G>A	p.Val830Met	missense_variant	12/13		NM_015144.3	ENSP00000499622	P1
ZCCHC14	ENST00000268616.9 linkuse as main transcript	c.2077G>A	p.Val693Met	missense_variant	12/13	1		ENSP00000268616		Q8WYQ9-1
ZCCHC14	ENST00000568020.6 linkuse as main transcript	c.2110G>A	p.Val704Met	missense_variant, NMD_transcript_variant	12/14	1		ENSP00000455431
ZCCHC14	ENST00000561928.1 linkuse as main transcript	c.1729G>A	p.Val577Met	missense_variant	10/10	5		ENSP00000456499

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86689

AN:

151966

Hom.:

29056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.653

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.712

Gnomad FIN

AF:

0.772

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.761

Gnomad OTH

AF:

0.569

GnomAD3 exomes

AF:

0.641

AC:

159332

AN:

248414

Hom.:

55359

AF XY:

0.660

AC XY:

88947

AN XY:

134738

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.476

Gnomad ASJ exome

AF:

0.664

Gnomad EAS exome

AF:

0.306

Gnomad SAS exome

AF:

0.727

Gnomad FIN exome

AF:

0.771

Gnomad NFE exome

AF:

0.757

Gnomad OTH exome

AF:

0.666

GnomAD4 exome

AF:

0.726

AC:

1061695

AN:

1461680

Hom.:

398011

Cov.:

AF XY:

0.727

AC XY:

528957

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.486

Gnomad4 ASJ exome

AF:

0.666

Gnomad4 EAS exome

AF:

0.314

Gnomad4 SAS exome

AF:

0.723

Gnomad4 FIN exome

AF:

0.772

Gnomad4 NFE exome

AF:

0.770

Gnomad4 OTH exome

AF:

0.675

GnomAD4 genome

AF:

0.570

AC:

86673

AN:

152084

Hom.:

29049

Cov.:

AF XY:

0.566

AC XY:

42053

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.544

Gnomad4 ASJ

AF:

0.653

Gnomad4 EAS

AF:

0.304

Gnomad4 SAS

AF:

0.714

Gnomad4 FIN

AF:

0.772

Gnomad4 NFE

AF:

0.761

Gnomad4 OTH

AF:

0.563

Alfa

AF:

0.708

Hom.:

89015

Bravo

AF:

0.531

TwinsUK

AF:

0.778

AC:

2886

ALSPAC

AF:

0.773

AC:

2978

ESP6500AA

AF:

0.241

AC:

1058

ESP6500EA

AF:

0.761

AC:

6540

ExAC

AF:

0.644

AC:

78109

Asia WGS

AF:

0.457

AC:

1590

AN:

3478

EpiCase

AF:

0.741

EpiControl

AF:

0.739

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.90

MetaRNN

Benign

0.0000018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.24

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.46

REVEL

Benign

0.090

Sift

Pathogenic

0.0

Sift4G

Benign

0.098

Polyphen

1.0

Vest4

0.066

MPC

0.84

ClinPred

0.017

GERP RS

4.5

Varity_R

0.22

gMVP

0.35

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