14-88568112-G-A

Variant names:

• chr14-88568112-G-A
• rs955426931
• NM_024824.5:c.153G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024824.5(ZC3H14):​c.153G>A​(p.Leu51Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L51L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZC3H14 NM_024824.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.598 with no splicing effect.

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.153G>A	p.Leu51Leu	synonymous	Exon 3 of 17	NP_079100.2
	ZC3H14	NM_001160103.2		c.153G>A	p.Leu51Leu	synonymous	Exon 3 of 17	NP_001153575.1	Q6PJT7-2
	ZC3H14	NM_001326310.2		c.153G>A	p.Leu51Leu	synonymous	Exon 3 of 17	NP_001313239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H14	ENST00000251038.10	TSL:1 MANE Select	c.153G>A	p.Leu51Leu	synonymous	Exon 3 of 17	ENSP00000251038.5	Q6PJT7-1
	ZC3H14	ENST00000302216.12	TSL:1	c.153G>A	p.Leu51Leu	synonymous	Exon 3 of 14	ENSP00000307025.8	Q6PJT7-3
	ZC3H14	ENST00000336693.8	TSL:1	c.51G>A	p.Leu17Leu	synonymous	Exon 3 of 15	ENSP00000338002.4	Q6PJT7-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.6
DANN	Benign	0.70
PhyloP100		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs955426931; hg19: chr14-89034456;