rs199820387

Variant names:

• chr14-88563662-G-A
• rs199820387
• NM_024824.5:c.48G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The ENST00000251038.10(ZC3H14):​c.48G>A​(p.Lys16Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000467 in 1,614,118 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00047 (1 hom.)
• Consequence: ZC3H14 ENST00000251038.10 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.26
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 14-88563662-G-A is Benign according to our data. Variant chr14-88563662-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 212625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.26 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000251038.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H14	NM_024824.5	MANE Select	c.48G>A	p.Lys16Lys	synonymous	Exon 2 of 17	NP_079100.2
	ZC3H14	NM_001160103.2		c.48G>A	p.Lys16Lys	synonymous	Exon 2 of 17	NP_001153575.1
	ZC3H14	NM_001326310.2		c.48G>A	p.Lys16Lys	synonymous	Exon 2 of 17	NP_001313239.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H14	ENST00000251038.10	TSL:1 MANE Select	c.48G>A	p.Lys16Lys	synonymous	Exon 2 of 17	ENSP00000251038.5
	ZC3H14	ENST00000302216.12	TSL:1	c.48G>A	p.Lys16Lys	synonymous	Exon 2 of 14	ENSP00000307025.8
	ZC3H14	ENST00000336693.8	TSL:1	c.-55G>A		5_prime_UTR	Exon 2 of 15	ENSP00000338002.4

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152266 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000749

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000286 AC: 72 AN: 251472 AF XY: 0.000287

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000571

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000475 AC: 694 AN: 1461852 Hom.: 1 Cov.: 31 AF XY: 0.000462 AC XY: 336 AN XY: 727224

African (AFR) AF: 0.000239 AC: 8 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000589 AC: 655 AN: 1111986

Other (OTH) AF: 0.000397 AC: 24 AN: 60394

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152266 Hom.: 0 Cov.: 33 AF XY: 0.000323 AC XY: 24 AN XY: 74398

African (AFR) AF: 0.000121 AC: 5 AN: 41468

American (AMR) AF: 0.000196 AC: 3 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000749 AC: 51 AN: 68046

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000594 Hom.: 0

Bravo AF: 0.000382

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000593

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		1.3
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=285/15	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: rs199820387; hg19: chr14-89030006;