Variant 16-87412145-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015144.3(ZCCHC14):c.2576C>T(p.Thr859Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T859S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

ZCCHC14
NM_015144.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.825

Variant links:

Genes affected

ZCCHC14 (HGNC:24134): (zinc finger CCHC-type containing 14) Predicted to enable nucleic acid binding activity; phosphatidylinositol binding activity; and zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZCCHC14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10329455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZCCHC14	NM_015144.3 linkuse as main transcript	c.2576C>T	p.Thr859Met	missense_variant	12/13	ENST00000671377.2
ZCCHC14	XM_005255858.4 linkuse as main transcript	c.2576C>T	p.Thr859Met	missense_variant	12/12
ZCCHC14	XM_017023082.3 linkuse as main transcript	c.2057C>T	p.Thr686Met	missense_variant	12/12
ZCCHC14	XR_243401.4 linkuse as main transcript	n.3362C>T		non_coding_transcript_exon_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZCCHC14	ENST00000671377.2 linkuse as main transcript	c.2576C>T	p.Thr859Met	missense_variant	12/13		NM_015144.3	P1
ZCCHC14	ENST00000268616.9 linkuse as main transcript	c.2165C>T	p.Thr722Met	missense_variant	12/13	1			Q8WYQ9-1
ZCCHC14	ENST00000568020.6 linkuse as main transcript	c.2198C>T	p.Thr733Met	missense_variant, NMD_transcript_variant	12/14	1
ZCCHC14	ENST00000561928.1 linkuse as main transcript	c.1817C>T	p.Thr606Met	missense_variant	10/10	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250632

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461630

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.2165C>T (p.T722M) alteration is located in exon 12 (coding exon 12) of the ZCCHC14 gene. This alteration results from a C to T substitution at nucleotide position 2165, causing the threonine (T) at amino acid position 722 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.38

M_CAP

Benign

0.019

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.7

REVEL

Benign

0.13

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.26

MutPred

0.085

Loss of glycosylation at T722 (P = 0.0393);

MVP

0.068

MPC

0.81

ClinPred

0.24

GERP RS

3.5

Varity_R

0.034

gMVP

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over