Variant chr3-42906406-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_207404.4(ZNF662):c.-94+238C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000412 in 1,506,310 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 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ZNF662
NM_207404.4 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.959

Variant links:

Genes affected

ZNF662 (HGNC:31930): (zinc finger protein 662) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF662 links:

ENSG00000290317 (HGNC:):

ENSG00000290317 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=0.006896049).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF662	NM_207404.4 linkuse as main transcript	c.-94+238C>T		intron_variant		ENST00000440367.7	NP_997287.2	Q6ZS27-1
ZNF662	NM_001134656.2 linkuse as main transcript	c.55C>T	p.Leu19Phe	missense_variant	1/4		NP_001128128.1	Q6ZS27-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF662	ENST00000440367.7 linkuse as main transcript	c.-94+238C>T		intron_variant		2	NM_207404.4	ENSP00000405047.2		Q6ZS27-1
ENSG00000290317	ENST00000426937.5 linkuse as main transcript	c.-163-2387C>T		intron_variant		3		ENSP00000413859.1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000958

AC:

AN:

104348

Hom.:

AF XY:

0.0000173

AC XY:

AN XY:

57970

show subpopulations

Gnomad AFR exome

AF:

0.000355

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.0000170

AC:

AN:

1353966

Hom.:

Cov.:

AF XY:

0.0000120

AC XY:

AN XY:

666274

show subpopulations

Gnomad4 AFR exome

AF:

0.000746

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000356

GnomAD4 genome

AF:

0.000256

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000219

ExAC

AF:

0.000168

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

Oct 05, 2023

The c.55C>T (p.L19F) alteration is located in exon 1 (coding exon 1) of the ZNF662 gene. This alteration results from a C to T substitution at nucleotide position 55, causing the leucine (L) at amino acid position 19 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

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.6

DANN

Uncertain

0.98

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.27

M_CAP

Benign

0.0011

MetaRNN

Benign

0.0069

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.75

REVEL

Benign

0.042

Sift

Uncertain

0.024

Sift4G

Pathogenic

0.0

Vest4

0.061

MutPred

0.42

Loss of disorder (P = 0.1424);

MVP

0.048

MPC

0.12

ClinPred

0.13

GERP RS

2.1

gMVP

0.096

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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