Genetic Variant ZCCHC7:p.Ser200Phe (chr9-37126931-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_032226.3(ZCCHC7):c.599C>T(p.Ser200Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 1,613,326 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 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZCCHC7
NM_032226.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.42

Variant links:

Genes affected

ZCCHC7 (HGNC:26209): (zinc finger CCHC-type containing 7) Enables RNA binding activity. Located in cytosol and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ZCCHC7 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=0.036441237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZCCHC7	NM_032226.3 link	c.599C>T	p.Ser200Phe	missense_variant	Exon 2 of 9	ENST00000336755.10	NP_115602.2	Q8N3Z6-1Q05DN1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZCCHC7	ENST00000336755.10 link	c.599C>T	p.Ser200Phe	missense_variant	Exon 2 of 9	2	NM_032226.3	ENSP00000337839.5	Q8N3Z6-1
ZCCHC7	ENST00000534928.5 link	c.599C>T	p.Ser200Phe	missense_variant	Exon 2 of 9	1		ENSP00000443113.2	Q8N3Z6-1
ZCCHC7	ENST00000322831.6 link	c.596C>T	p.Ser199Phe	missense_variant	Exon 3 of 4	1		ENSP00000316365.6	X6R4A7
ZCCHC7	ENST00000461038.5 link	n.879C>T		non_coding_transcript_exon_variant	Exon 2 of 9	1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000797

AC:

AN:

250836

Hom.:

AF XY:

0.0000959

AC XY:

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00103

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461090

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000630

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00231

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000162

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.599C>T (p.S200F) alteration is located in exon 2 (coding exon 1) of the ZCCHC7 gene. This alteration results from a C to T substitution at nucleotide position 599, causing the serine (S) at amino acid position 200 to be replaced by a phenylalanine (F). 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

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.046

T;T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

.;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.036

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.3

M;M;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.4

N;.;N

REVEL

Benign

0.20

Sift

Uncertain

0.021

D;.;D

Sift4G

Benign

0.14

T;T;D

Polyphen

0.98

D;D;.

Vest4

0.35

MVP

0.47

MPC

0.34

ClinPred

0.22

GERP RS

5.5

Varity_R

0.12

gMVP

0.55

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