rs8007288

Variant names:

• chr14-88587530-A-G
• rs8007288
• NM_024824.5:c.1280-9204A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024824.5(ZC3H14):​c.1280-9204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,984 control chromosomes in the GnomAD database, including 10,487 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (10487 hom., cov: 32)
• Consequence: ZC3H14 NM_024824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H14	NM_024824.5	MANE Select	c.1280-9204A>G		intron	N/A	NP_079100.2
	ZC3H14	NM_001160103.2		c.1280-9204A>G		intron	N/A	NP_001153575.1	Q6PJT7-2
	ZC3H14	NM_001326310.2		c.1280-9204A>G		intron	N/A	NP_001313239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H14	ENST00000251038.10	TSL:1 MANE Select	c.1280-9204A>G		intron	N/A	ENSP00000251038.5	Q6PJT7-1
	ZC3H14	ENST00000556000.5	TSL:1	c.1025-9204A>G		intron	N/A	ENSP00000451054.1	H0YJA2
	ZC3H14	ENST00000302216.12	TSL:1	c.1279+9390A>G		intron	N/A	ENSP00000307025.8	Q6PJT7-3

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50333 AN: 151864 Hom.: 10491 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.0469

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50307 AN: 151984 Hom.: 10487 Cov.: 32 AF XY: 0.333 AC XY: 24704 AN XY: 74262

African (AFR) AF: 0.103 AC: 4251 AN: 41470

American (AMR) AF: 0.326 AC: 4980 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1534 AN: 3472

East Asian (EAS) AF: 0.0465 AC: 240 AN: 5166

South Asian (SAS) AF: 0.250 AC: 1206 AN: 4820

European-Finnish (FIN) AF: 0.524 AC: 5516 AN: 10536

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31386 AN: 67942

Other (OTH) AF: 0.377 AC: 794 AN: 2108

Alfa AF: 0.396 Hom.: 1690

Bravo AF: 0.305

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.42
PhyloP100		-0.67
Mutation Taster		=100/0	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: rs8007288; hg19: chr14-89053874;