Variant chr19-32353353-G-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_001136156.2(ZNF507):c.523G>T(p.Val175Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ZNF507
NM_001136156.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.758

Variant links:

Genes affected

ZNF507 (HGNC:23783): (zinc finger protein 507) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF507 links:

ZNF507 (HGNC:):

ZNF507 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=0.051507264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF507	NM_001136156.2 linkuse as main transcript	c.523G>T	p.Val175Leu	missense_variant	3/7	ENST00000355898.6	NP_001129628.1	Q8TCN5-1
ZNF507	NM_014910.5 linkuse as main transcript	c.523G>T	p.Val175Leu	missense_variant	2/6		NP_055725.2	Q8TCN5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF507	ENST00000355898.6 linkuse as main transcript	c.523G>T	p.Val175Leu	missense_variant	3/7	1	NM_001136156.2	ENSP00000348162.4	Q8TCN5-1
ZNF507	ENST00000544431.5 linkuse as main transcript	c.523G>T	p.Val175Leu	missense_variant	3/8	1		ENSP00000441549.1	B9EGE7
ZNF507	ENST00000311921.8 linkuse as main transcript	c.523G>T	p.Val175Leu	missense_variant	2/6	1		ENSP00000312277.2	Q8TCN5-1
ZNF507	ENST00000587084.5 linkuse as main transcript	n.778G>T		non_coding_transcript_exon_variant	3/4	1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251446

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000318

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:

0.000326

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000313

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:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

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

Bravo

AF:

0.0000264

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

Jan 19, 2022

The c.523G>T (p.V175L) alteration is located in exon 3 (coding exon 1) of the ZNF507 gene. This alteration results from a G to T substitution at nucleotide position 523, causing the valine (V) at amino acid position 175 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

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.038

T;.;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.69

.;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

L;.;L

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.070

N;N;N

REVEL

Benign

0.053

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.078

MutPred

0.20

Gain of catalytic residue at V175 (P = 0.0547);Gain of catalytic residue at V175 (P = 0.0547);Gain of catalytic residue at V175 (P = 0.0547);

MVP

0.21

MPC

0.054

ClinPred

0.037

GERP RS

2.4

Varity_R

0.023

gMVP

0.12

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