14-88620934-TAAAAAA-TAAAAAAA

Variant names:

• chr14-88620934-T-TA
• rs35953031
• NM_024824.5:c.*9200dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024824.5(ZC3H14):​c.*9200dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (22455 hom., cov: 0)
  • Exomes 𝑓: 0.32 (71 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZC3H14 NM_024824.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.252
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 14-88620934-T-TA is Benign according to our data. Variant chr14-88620934-T-TA is described in ClinVar as Benign. ClinVar VariationId is 402826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H14	NM_024824.5	c.*9200dupA		3_prime_UTR_variant	Exon 17 of 17	ENST00000251038.10	NP_079100.2
EML5	NM_183387.3	c.5203-9dupT		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.*9200dupA		3_prime_UTR_variant	Exon 17 of 17	1	NM_024824.5	ENSP00000251038.5
EML5	ENST00000554922.6	c.5203-9dupT		intron_variant	Intron 38 of 43	5	NM_183387.3	ENSP00000451998.1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 78593 AN: 138858 Hom.: 22462 Cov.: 0

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.632

GnomAD2 exomes AF: 0.250 AC: 13083 AN: 52316 AF XY: 0.245

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.223

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.260

Gnomad OTH exome AF: 0.280

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.322 AC: 392122 AN: 1218028 Hom.: 71 Cov.: 0 AF XY: 0.319 AC XY: 189271 AN XY: 593774

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

African (AFR) AF: 0.231 AC: 6107 AN: 26466

American (AMR) AF: 0.305 AC: 5109 AN: 16736

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 6079 AN: 18422

East Asian (EAS) AF: 0.236 AC: 7743 AN: 32764

South Asian (SAS) AF: 0.236 AC: 13538 AN: 57298

European-Finnish (FIN) AF: 0.295 AC: 10716 AN: 36340

Middle Eastern (MID) AF: 0.367 AC: 1780 AN: 4854

European-Non Finnish (NFE) AF: 0.334 AC: 325339 AN: 974674

Other (OTH) AF: 0.311 AC: 15711 AN: 50474

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.566 AC: 78572 AN: 138864 Hom.: 22455 Cov.: 0 AF XY: 0.568 AC XY: 37881 AN XY: 66710

African (AFR) AF: 0.429 AC: 16044 AN: 37374

American (AMR) AF: 0.657 AC: 9088 AN: 13834

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2314 AN: 3368

East Asian (EAS) AF: 0.491 AC: 2345 AN: 4776

South Asian (SAS) AF: 0.496 AC: 2120 AN: 4270

European-Finnish (FIN) AF: 0.625 AC: 4621 AN: 7398

Middle Eastern (MID) AF: 0.699 AC: 186 AN: 266

European-Non Finnish (NFE) AF: 0.620 AC: 40192 AN: 64814

Other (OTH) AF: 0.635 AC: 1191 AN: 1876

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;