rs3748400

chr16-87412233-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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]

ACMG classification

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	UniProt
ZCCHC14	NM_015144.3	c.2488G>A	p.Val830Met	missense_variant	12/13	ENST00000671377.2
ZCCHC14	XM_005255858.4	c.2488G>A	p.Val830Met	missense_variant	12/12
ZCCHC14	XM_017023082.3	c.1969G>A	p.Val657Met	missense_variant	12/12
ZCCHC14	XR_243401.4	n.3274G>A		non_coding_transcript_exon_variant	12/14

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86689 AN: 151966 Hom.: 29056 Cov.: 32

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

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.: 96 AF XY: 0.727 AC XY: 528957 AN XY: 727156

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.: 32 AF XY: 0.566 AC XY: 42053 AN XY: 74334

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	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.90	D
MetaRNN	Benign	0.0000018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	0.24	P
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.090
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.098	T
Polyphen		1.0	D
Vest4		0.066
MPC		0.84
ClinPred		0.017	T
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

Other links and lift over

dbSNP: rs3748400; hg19: chr16-87445839; COSMIC: COSV51884359; COSMIC: COSV51884359;