Genetic Variant ZNF671:p.Glu515Lys (chr19-57720543-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_024833.3(ZNF671):c.1543G>A(p.Glu515Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ZNF671
NM_024833.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.39

Variant links:

Genes affected

ZNF671 (HGNC:26279): (zinc finger protein 671) 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]

ZNF671 links:

ENSG00000269026 (HGNC:):

ENSG00000269026 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=0.037302792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF671	NM_024833.3 link	c.1543G>A	p.Glu515Lys	missense_variant	Exon 4 of 4	ENST00000317398.10	NP_079109.2	Q8TAW3
ZNF671	NM_001321376.2 link	c.1312G>A	p.Glu438Lys	missense_variant	Exon 5 of 5		NP_001308305.1
ZNF671	NM_001321375.2 link	c.1249G>A	p.Glu417Lys	missense_variant	Exon 3 of 3		NP_001308304.1	B7Z1N1
ZNF671	XM_017027314.2 link	c.1312G>A	p.Glu438Lys	missense_variant	Exon 4 of 4		XP_016882803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF671	ENST00000317398.10 link	c.1543G>A	p.Glu515Lys	missense_variant	Exon 4 of 4	1	NM_024833.3	ENSP00000321848.5		Q8TAW3
ENSG00000269026	ENST00000594684.1 link	c.34-30242C>T		intron_variant	Intron 1 of 2	1		ENSP00000472160.1		M0R1X1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

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:

0.000192

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:

0.000103

AC:

AN:

251314

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00130

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:

0.0000130

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1543G>A (p.E515K) alteration is located in exon 4 (coding exon 4) of the ZNF671 gene. This alteration results from a G to A substitution at nucleotide position 1543, causing the glutamic acid (E) at amino acid position 515 to be replaced by a lysine (K). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.73

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.79

M_CAP

Benign

0.0028

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.28

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.60

REVEL

Benign

0.070

Sift

Benign

0.047

Sift4G

Benign

0.17

Polyphen

0.63

Vest4

0.14

MutPred

0.58

Gain of methylation at E515 (P = 0.0016);

MVP

0.33

MPC

0.28

ClinPred

0.049

GERP RS

-3.8

Varity_R

0.048

gMVP

0.085

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