14-88620934-TAAAAAA-TAAA

Variant names:

• chr14-88620934-TAAA-T
• rs35953031
• NM_024824.5:c.*9198_*9200delAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024824.5(ZC3H14):​c.*9198_*9200delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,362,000 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 0.000072 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0019 (0 hom.)
• Consequence: ZC3H14 NM_024824.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H14	NM_024824.5	c.*9198_*9200delAAA		3_prime_UTR_variant	Exon 17 of 17	ENST00000251038.10	NP_079100.2
EML5	NM_183387.3	c.5203-11_5203-9delTTT		intron_variant	Intron 38 of 43	ENST00000554922.6	NP_899243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H14	ENST00000251038.10	c.*9198_*9200delAAA		3_prime_UTR_variant	Exon 17 of 17	1	NM_024824.5	ENSP00000251038.5
EML5	ENST00000554922.6	c.5203-11_5203-9delTTT		intron_variant	Intron 38 of 43	5	NM_183387.3	ENSP00000451998.1

Frequencies

GnomAD3 genomes AF: 0.0000720 AC: 10 AN: 138850 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000145

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000407

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000617

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0130 AC: 681 AN: 52316 Hom.: 0 AF XY: 0.0148 AC XY: 389 AN XY: 26334

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.0162

Gnomad ASJ exome AF: 0.0164

Gnomad EAS exome AF: 0.0166

Gnomad SAS exome AF: 0.0272

Gnomad FIN exome AF: 0.00380

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.00880

GnomAD4 exome AF: 0.00188 AC: 2305 AN: 1223150 Hom.: 0 AF XY: 0.00208 AC XY: 1241 AN XY: 596020

Gnomad4 AFR exome AF: 0.00245

Gnomad4 AMR exome AF: 0.00696

Gnomad4 ASJ exome AF: 0.00298

Gnomad4 EAS exome AF: 0.00357

Gnomad4 SAS exome AF: 0.00834

Gnomad4 FIN exome AF: 0.00201

Gnomad4 NFE exome AF: 0.00132

Gnomad4 OTH exome AF: 0.00195

GnomAD4 genome AF: 0.0000720 AC: 10 AN: 138850 Hom.: 0 Cov.: 0 AF XY: 0.0000750 AC XY: 5 AN XY: 66668

Gnomad4 AFR AF: 0.0000268

Gnomad4 AMR AF: 0.000145

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000407

Gnomad4 NFE AF: 0.0000617

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs35953031; hg19: chr14-89087278;