Variant 19-37698833-C-A 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_032689.5(ZNF607):c.1298G>T(p.Arg433Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,611,760 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. R433H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZNF607
NM_032689.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.92

Variant links:

Genes affected

ZNF607 (HGNC:28192): (zinc finger protein 607) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF607 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=0.04218644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF607	NM_032689.5 linkuse as main transcript	c.1298G>T	p.Arg433Leu	missense_variant	5/5	ENST00000355202.9	NP_116078.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF607	ENST00000355202.9 linkuse as main transcript	c.1298G>T	p.Arg433Leu	missense_variant	5/5	2	NM_032689.5	ENSP00000347338		Q96SK3-1
ZNF607	ENST00000395835.7 linkuse as main transcript	c.1295G>T	p.Arg432Leu	missense_variant	5/5	2		ENSP00000438015	P1	Q96SK3-3

Frequencies

GnomAD3 genomes

AF:

0.000167

AC:

AN:

149800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000492

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00140

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:

0.000978

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251432

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

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:

0.000489

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000268

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:

0.000149

GnomAD4 genome

AF:

0.000167

AC:

AN:

149924

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

73248

show subpopulations

Gnomad4 AFR

AF:

0.0000490

Gnomad4 AMR

AF:

0.00140

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:

0.000965

Bravo

AF:

0.000540

ExAC

AF:

0.00000824

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

Jul 15, 2021

The c.1298G>T (p.R433L) alteration is located in exon 5 (coding exon 4) of the ZNF607 gene. This alteration results from a G to T substitution at nucleotide position 1298, causing the arginine (R) at amino acid position 433 to be replaced by a leucine (L). 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

0.31

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.0

DANN

Benign

0.94

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.28

T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.010

Sift

Benign

0.47

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.17

B;.

Vest4

0.13

MutPred

0.38

Loss of catalytic residue at R433 (P = 0.0042);.;

MVP

0.11

MPC

0.058

ClinPred

0.043

GERP RS

-2.8

Varity_R

0.065

gMVP

0.023

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