chr14-88568130-C-A

Variant names:

• chr14-88568130-C-A
• rs764670721
• NM_024824.5:c.171C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024824.5(ZC3H14):​c.171C>A​(p.Asn57Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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 the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZC3H14 NM_024824.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86
• Publications: 0 publications found

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]

ZC3H14 Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• intellectual disability, autosomal recessive 56

  Inheritance: AR, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36571294).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024824.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H14	NM_024824.5	MANE Select	c.171C>A	p.Asn57Lys	missense	Exon 3 of 17	NP_079100.2
	ZC3H14	NM_001160103.2		c.171C>A	p.Asn57Lys	missense	Exon 3 of 17	NP_001153575.1
	ZC3H14	NM_001326310.2		c.171C>A	p.Asn57Lys	missense	Exon 3 of 17	NP_001313239.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H14	ENST00000251038.10	TSL:1 MANE Select	c.171C>A	p.Asn57Lys	missense	Exon 3 of 17	ENSP00000251038.5
	ZC3H14	ENST00000302216.12	TSL:1	c.171C>A	p.Asn57Lys	missense	Exon 3 of 14	ENSP00000307025.8
	ZC3H14	ENST00000336693.8	TSL:1	c.69C>A	p.Asn23Lys	missense	Exon 3 of 15	ENSP00000338002.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.79	N
PhyloP100		5.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.31
Sift	Benign	0.072	T
Sift4G	Uncertain	0.028	D
Polyphen		0.98	D
Vest4		0.45
MutPred		0.46		Gain of methylation at N57 (P = 0.0283)
MVP		0.093
MPC		2.4
ClinPred		0.95	D
GERP RS		5.6
Varity_R		0.26
gMVP		0.36
Mutation Taster		=67/33	polymorphism

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: rs764670721; hg19: chr14-89034474;