14-88620934-TAAAAAA-TAAAA

Variant names:

• chr14-88620934-TAA-T
• rs35953031
• NM_024824.5:c.*9199_*9200delAA

Variant summary

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

The NM_024824.5(ZC3H14):​c.*9199_*9200delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,320,434 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 0)
  • Exomes 𝑓: 0.022 (0 hom.)
• Consequence: ZC3H14 NM_024824.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826
• 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]

EML5 (HGNC:18197): (EMAP like 5) Predicted to enable microtubule binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

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.*9199_*9200delAA		3_prime_UTR	Exon 17 of 17	NP_079100.2
	EML5	NM_183387.3	MANE Select	c.5203-10_5203-9delTT		intron	N/A	NP_899243.1	Q05BV3-5
	ZC3H14	NM_001160103.2		c.*9199_*9200delAA		3_prime_UTR	Exon 17 of 17	NP_001153575.1	Q6PJT7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H14	ENST00000251038.10	TSL:1 MANE Select	c.*9199_*9200delAA		3_prime_UTR	Exon 17 of 17	ENSP00000251038.5	Q6PJT7-1
	EML5	ENST00000554922.6	TSL:5 MANE Select	c.5203-10_5203-9delTT		intron	N/A	ENSP00000451998.1	Q05BV3-5
	EML5	ENST00000380664.9	TSL:5	c.5179-10_5179-9delTT		intron	N/A	ENSP00000370039.5	Q05BV3-1

Frequencies

GnomAD3 genomes AF: 0.000440 AC: 61 AN: 138782 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000435

Gnomad ASJ AF: 0.000594

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00218

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000401

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0623 AC: 3258 AN: 52316 AF XY: 0.0677

Gnomad AFR exome AF: 0.0715

Gnomad AMR exome AF: 0.0760

Gnomad ASJ exome AF: 0.0606

Gnomad EAS exome AF: 0.0850

Gnomad FIN exome AF: 0.0237

Gnomad NFE exome AF: 0.0550

Gnomad OTH exome AF: 0.0543

GnomAD4 exome AF: 0.0218 AC: 25805 AN: 1181652 Hom.: 0 AF XY: 0.0230 AC XY: 13257 AN XY: 575540

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

African (AFR) AF: 0.0329 AC: 836 AN: 25376

American (AMR) AF: 0.0402 AC: 646 AN: 16050

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 378 AN: 17704

East Asian (EAS) AF: 0.0329 AC: 1016 AN: 30914

South Asian (SAS) AF: 0.0529 AC: 2924 AN: 55266

European-Finnish (FIN) AF: 0.0222 AC: 773 AN: 34872

Middle Eastern (MID) AF: 0.0153 AC: 73 AN: 4758

European-Non Finnish (NFE) AF: 0.0191 AC: 18091 AN: 948038

Other (OTH) AF: 0.0219 AC: 1068 AN: 48674

⚠️ 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: 0.000440 AC: 61 AN: 138782 Hom.: 0 Cov.: 0 AF XY: 0.000465 AC XY: 31 AN XY: 66616

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

African (AFR) AF: 0.000295 AC: 11 AN: 37348

American (AMR) AF: 0.000435 AC: 6 AN: 13806

Ashkenazi Jewish (ASJ) AF: 0.000594 AC: 2 AN: 3366

East Asian (EAS) AF: 0.00 AC: 0 AN: 4794

South Asian (SAS) AF: 0.00 AC: 0 AN: 4296

European-Finnish (FIN) AF: 0.00218 AC: 16 AN: 7346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000401 AC: 26 AN: 64784

Other (OTH) AF: 0.00 AC: 0 AN: 1870

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35953031; hg19: chr14-89087278;