14-88596823-A-G

Variant names:

• chr14-88596823-A-G
• rs2297124
• NM_024824.5:c.1354+15A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024824.5(ZC3H14):​c.1354+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 1,611,292 control chromosomes in the GnomAD database, including 606,639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55510 hom., cov: 31)
  • Exomes 𝑓: 0.87 (551129 hom.)
• Consequence: ZC3H14 NM_024824.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.822
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 14-88596823-A-G is Benign according to our data. Variant chr14-88596823-A-G is described in ClinVar as Benign. ClinVar VariationId is 1684249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H14	NM_024824.5	c.1354+15A>G		intron_variant	Intron 10 of 16	ENST00000251038.10	NP_079100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H14	ENST00000251038.10	c.1354+15A>G		intron_variant	Intron 10 of 16	1	NM_024824.5	ENSP00000251038.5

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129557 AN: 152014 Hom.: 55454 Cov.: 31

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.880

GnomAD2 exomes AF: 0.871 AC: 218848 AN: 251158 AF XY: 0.864

Gnomad AFR exome AF: 0.776

Gnomad AMR exome AF: 0.945

Gnomad ASJ exome AF: 0.914

Gnomad EAS exome AF: 0.918

Gnomad FIN exome AF: 0.900

Gnomad NFE exome AF: 0.878

Gnomad OTH exome AF: 0.881

GnomAD4 exome AF: 0.868 AC: 1266563 AN: 1459160 Hom.: 551129 Cov.: 33 AF XY: 0.865 AC XY: 628092 AN XY: 726090

African (AFR) AF: 0.771 AC: 25761 AN: 33404

American (AMR) AF: 0.942 AC: 42120 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 23911 AN: 26112

East Asian (EAS) AF: 0.942 AC: 37378 AN: 39664

South Asian (SAS) AF: 0.749 AC: 64573 AN: 86182

European-Finnish (FIN) AF: 0.899 AC: 47965 AN: 53374

Middle Eastern (MID) AF: 0.873 AC: 5032 AN: 5764

European-Non Finnish (NFE) AF: 0.872 AC: 967714 AN: 1109652

Other (OTH) AF: 0.864 AC: 52109 AN: 60284

GnomAD4 genome AF: 0.852 AC: 129670 AN: 152132 Hom.: 55510 Cov.: 31 AF XY: 0.854 AC XY: 63508 AN XY: 74356

African (AFR) AF: 0.773 AC: 32059 AN: 41460

American (AMR) AF: 0.910 AC: 13920 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3180 AN: 3470

East Asian (EAS) AF: 0.924 AC: 4770 AN: 5160

South Asian (SAS) AF: 0.768 AC: 3697 AN: 4814

European-Finnish (FIN) AF: 0.907 AC: 9606 AN: 10588

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.875 AC: 59550 AN: 68032

Other (OTH) AF: 0.881 AC: 1861 AN: 2112

Alfa AF: 0.879 Hom.: 10496

Bravo AF: 0.854

Asia WGS AF: 0.858 AC: 2987 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Intellectual disability, autosomal recessive 56 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.073
DANN	Benign	0.28
PhyloP100		-0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2297124; hg19: chr14-89063167; COSMIC: COSV107229784; COSMIC: COSV107229784;