Variant 5-132998782-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001300816.3(ZCCHC10):c.380G>A(p.Ser127Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00053 in 1,614,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 0 hom. )

Consequence

ZCCHC10
NM_001300816.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.55

Variant links:

Genes affected

ZCCHC10 (HGNC:25954): (zinc finger CCHC-type containing 10) Predicted to enable nucleic acid binding activity and zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZCCHC10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05691755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC10	NM_001300816.3 link	c.380G>A	p.Ser127Asn	missense_variant	5/5	ENST00000509437.6	NP_001287745.1	Q8TBK6-1B4DU89

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCCHC10	ENST00000509437.6 link	c.380G>A	p.Ser127Asn	missense_variant	5/5	1	NM_001300816.3	ENSP00000423276.1		Q8TBK6-1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000823

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000247

AC:

AN:

251420

Hom.:

AF XY:

0.000272

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000510

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000545

AC:

796

AN:

1461866

Hom.:

Cov.:

AF XY:

0.000472

AC XY:

343

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000682

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000387

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000469

Hom.:

Bravo

AF:

0.000393

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000214

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000593

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

Apr 01, 2024

The c.314G>A (p.S105N) alteration is located in exon 4 (coding exon 4) of the ZCCHC10 gene. This alteration results from a G to A substitution at nucleotide position 314, causing the serine (S) at amino acid position 105 to be replaced by an asparagine (N). 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

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

.;T;T;T

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.74

T;T;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.057

T;T;T;T

MetaSVM

Uncertain

-0.051

MutationAssessor

Uncertain

2.2

.;.;M;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

0.99

D;.;D;D

Vest4

0.38

MVP

0.030

MPC

0.17

ClinPred

0.13

GERP RS

4.8

Varity_R

0.34

gMVP

0.28

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