chr14-88571138-C-CATTTT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_024824.5(ZC3H14):​c.235+14_235+15insATTTT 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: not found (cov: 0)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: ZC3H14 NM_024824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• 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 0 ACMG points.

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

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1309972 Hom.: 0 Cov.: 18 AF XY: 0.00000153 AC XY: 1 AN XY: 652058

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

African (AFR) AF: 0.00 AC: 0 AN: 30736

American (AMR) AF: 0.0000251 AC: 1 AN: 39916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23422

East Asian (EAS) AF: 0.00 AC: 0 AN: 36806

South Asian (SAS) AF: 0.00 AC: 0 AN: 74840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5288

European-Non Finnish (NFE) AF: 0.00000201 AC: 2 AN: 996582

Other (OTH) AF: 0.00 AC: 0 AN: 54084

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10682918; hg19: chr14-89037482;