rs201108116

Positions:

• chr14-88578121-T-A
• chr14-88578121-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024824.5(ZC3H14):​c.1260T>A​(p.Asp420Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZC3H14 NM_024824.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

Genes affected

ZC3H14 (HGNC:20509): (zinc finger CCCH-type containing 14) The protein encoded by this gene is a poly(A)-binding protein that can affect gene expression and poly(A) tail length. The encoded protein may influence mRNA stability, nuclear export, and translation. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05568412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H14	NM_024824.5	c.1260T>A	p.Asp420Glu	missense_variant	9/17	ENST00000251038.10	NP_079100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3H14	ENST00000251038.10	c.1260T>A	p.Asp420Glu	missense_variant	9/17	1	NM_024824.5	ENSP00000251038	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250626 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135708

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

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: 6.84e-7 AC: 1 AN: 1461824 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.5
DANN	Benign	0.88
DEOGEN2	Benign	0.018	T;.;.;.;.;.;.;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.72	T;T;T;T;T;T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.056	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N;N;.;.;N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.090	N;N;N;N;N;N;N;.
REVEL	Benign	0.038
Sift	Benign	0.46	T;T;T;T;T;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T
Polyphen		0.0040	B;B;B;.;.;.;.;.
Vest4		0.082
MutPred		0.14		Gain of loop (P = 0.024);Gain of loop (P = 0.024);Gain of loop (P = 0.024);.;Gain of loop (P = 0.024);Gain of loop (P = 0.024);.;.;
MVP		0.043
MPC		0.071
ClinPred		0.034	T
GERP RS		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.080

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: rs201108116; hg19: chr14-89044465;