16-87412233-C-T

Variant names:

• chr16-87412233-C-T
• rs3748400
• NM_015144.3:c.2488G>A

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015144.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCCHC14	NM_015144.3	MANE Select	c.2488G>A	p.Val830Met	missense	Exon 12 of 13	NP_055959.2	A0A590UJW6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZCCHC14	ENST00000671377.2	MANE Select	c.2488G>A	p.Val830Met	missense	Exon 12 of 13	ENSP00000499622.1	A0A590UJW6
	ZCCHC14	ENST00000268616.9	TSL:1	c.2077G>A	p.Val693Met	missense	Exon 12 of 13	ENSP00000268616.4	Q8WYQ9-1
	ZCCHC14	ENST00000568020.6	TSL:1	n.2107G>A		non_coding_transcript_exon	Exon 12 of 14	ENSP00000455431.2	A0A5F9XIK1

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

GnomAD2 exomes AF: 0.641 AC: 159332 AN: 248414 AF XY: 0.660

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 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

African (AFR) AF: 0.201 AC: 6720 AN: 33480

American (AMR) AF: 0.486 AC: 21754 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 17400 AN: 26136

East Asian (EAS) AF: 0.314 AC: 12462 AN: 39700

South Asian (SAS) AF: 0.723 AC: 62380 AN: 86256

European-Finnish (FIN) AF: 0.772 AC: 41067 AN: 53222

Middle Eastern (MID) AF: 0.571 AC: 3290 AN: 5764

European-Non Finnish (NFE) AF: 0.770 AC: 855839 AN: 1112002

Other (OTH) AF: 0.675 AC: 40783 AN: 60396

GnomAD4 genome AF: 0.570 AC: 86673 AN: 152084 Hom.: 29049 Cov.: 32 AF XY: 0.566 AC XY: 42053 AN XY: 74334

African (AFR) AF: 0.221 AC: 9177 AN: 41480

American (AMR) AF: 0.544 AC: 8322 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2266 AN: 3472

East Asian (EAS) AF: 0.304 AC: 1572 AN: 5174

South Asian (SAS) AF: 0.714 AC: 3440 AN: 4820

European-Finnish (FIN) AF: 0.772 AC: 8163 AN: 10572

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51738 AN: 67974

Other (OTH) AF: 0.563 AC: 1184 AN: 2104

Alfa AF: 0.692 Hom.: 160012

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 v4.9

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
PhyloP100		1.4
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
Mutation Taster		=76/24	polymorphism (auto)

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

Other links and lift over

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