14-88571138-C-CA

Variant names:

• chr14-88571138-C-CA
• rs10682918
• NM_024824.5:c.235+14_235+15insA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_024824.5(ZC3H14):​c.235+14_235+15insA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.013 (15 hom.)
• Consequence: ZC3H14 NM_024824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 15 AR,AD gene

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.235+14_235+15insA		intron	N/A	NP_079100.2
	ZC3H14	NM_001160103.2		c.235+14_235+15insA		intron	N/A	NP_001153575.1	Q6PJT7-2
	ZC3H14	NM_001326310.2		c.235+14_235+15insA		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.235+14_235+15insA		intron	N/A	ENSP00000251038.5	Q6PJT7-1
	ZC3H14	ENST00000302216.12	TSL:1	c.235+14_235+15insA		intron	N/A	ENSP00000307025.8	Q6PJT7-3
	ZC3H14	ENST00000336693.8	TSL:1	c.133+14_133+15insA		intron	N/A	ENSP00000338002.4	Q6PJT7-4

Frequencies

GnomAD3 genomes AF: 0.000133 AC: 20 AN: 150674 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00127

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0118 AC: 2285 AN: 193698 AF XY: 0.0118

Gnomad AFR exome AF: 0.00335

Gnomad AMR exome AF: 0.00952

Gnomad ASJ exome AF: 0.0158

Gnomad EAS exome AF: 0.00796

Gnomad FIN exome AF: 0.00503

Gnomad NFE exome AF: 0.0146

Gnomad OTH exome AF: 0.0166

GnomAD4 exome AF: 0.0126 AC: 15711 AN: 1246888 Hom.: 15 Cov.: 18 AF XY: 0.0124 AC XY: 7665 AN XY: 619498

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00466 AC: 141 AN: 30286

American (AMR) AF: 0.00830 AC: 324 AN: 39014

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 286 AN: 22072

East Asian (EAS) AF: 0.00408 AC: 148 AN: 36260

South Asian (SAS) AF: 0.0152 AC: 1092 AN: 72060

European-Finnish (FIN) AF: 0.0115 AC: 525 AN: 45476

Middle Eastern (MID) AF: 0.00982 AC: 50 AN: 5092

European-Non Finnish (NFE) AF: 0.0133 AC: 12524 AN: 944952

Other (OTH) AF: 0.0120 AC: 621 AN: 51676

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000133 AC: 20 AN: 150778 Hom.: 0 Cov.: 0 AF XY: 0.0000951 AC XY: 7 AN XY: 73624

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000244 AC: 1 AN: 41022

American (AMR) AF: 0.000132 AC: 2 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4782

European-Finnish (FIN) AF: 0.00127 AC: 13 AN: 10272

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67668

Other (OTH) AF: 0.00 AC: 0 AN: 2100

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000280098), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0393 Hom.: 2617

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.3
Mutation Taster		=100/0	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: rs10682918; hg19: chr14-89037482;