chr14-88571138-C-CATT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_024824.5(ZC3H14):​c.235+14_235+15insATT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0050 (3 hom.)
• Consequence: ZC3H14 NM_024824.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -6 ACMG points.

• BP6: Variant 14-88571138-C-CATT is Benign according to our data. Variant chr14-88571138-C-CATT is described in ClinVar as Likely_benign. ClinVar VariationId is 445396.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 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+15insATT		intron	N/A	NP_079100.2
	ZC3H14	NM_001160103.2		c.235+14_235+15insATT		intron	N/A	NP_001153575.1	Q6PJT7-2
	ZC3H14	NM_001326310.2		c.235+14_235+15insATT		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+15insATT		intron	N/A	ENSP00000251038.5	Q6PJT7-1
	ZC3H14	ENST00000302216.12	TSL:1	c.235+14_235+15insATT		intron	N/A	ENSP00000307025.8	Q6PJT7-3
	ZC3H14	ENST00000336693.8	TSL:1	c.133+14_133+15insATT		intron	N/A	ENSP00000338002.4	Q6PJT7-4

Frequencies

GnomAD3 genomes AF: 0.000265 AC: 40 AN: 150722 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000587

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000194

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000207

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00279 AC: 541 AN: 193698 AF XY: 0.00273

Gnomad AFR exome AF: 0.00224

Gnomad AMR exome AF: 0.00355

Gnomad ASJ exome AF: 0.00387

Gnomad EAS exome AF: 0.00168

Gnomad FIN exome AF: 0.000995

Gnomad NFE exome AF: 0.00303

Gnomad OTH exome AF: 0.00306

GnomAD4 exome AF: 0.00503 AC: 6450 AN: 1283300 Hom.: 3 Cov.: 18 AF XY: 0.00485 AC XY: 3098 AN XY: 638518

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

African (AFR) AF: 0.00197 AC: 60 AN: 30518

American (AMR) AF: 0.00310 AC: 123 AN: 39634

Ashkenazi Jewish (ASJ) AF: 0.00449 AC: 103 AN: 22952

East Asian (EAS) AF: 0.00109 AC: 40 AN: 36618

South Asian (SAS) AF: 0.00557 AC: 412 AN: 73938

European-Finnish (FIN) AF: 0.00397 AC: 188 AN: 47328

Middle Eastern (MID) AF: 0.00326 AC: 17 AN: 5210

European-Non Finnish (NFE) AF: 0.00542 AC: 5276 AN: 974058

Other (OTH) AF: 0.00435 AC: 231 AN: 53044

⚠️ 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: 0.000265 AC: 40 AN: 150826 Hom.: 0 Cov.: 0 AF XY: 0.000217 AC XY: 16 AN XY: 73662

African (AFR) AF: 0.000585 AC: 24 AN: 41022

American (AMR) AF: 0.00 AC: 0 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: 4784

European-Finnish (FIN) AF: 0.000194 AC: 2 AN: 10284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000207 AC: 14 AN: 67702

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

Alfa AF: 0.0114 Hom.: 2617

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;