19-57720878-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024833.3(ZNF671):c.1208G>A(p.Gly403Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,614,124 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 49 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 50 hom. )

Consequence

ZNF671
NM_024833.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.769

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040881634).

BP6

Variant 19-57720878-C-T is Benign according to our data. Variant chr19-57720878-C-T is described in ClinVar as [Benign]. Clinvar id is 769060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2140/152230) while in subpopulation AFR AF= 0.0492 (2041/41520). AF 95% confidence interval is 0.0474. There are 49 homozygotes in gnomad4. There are 976 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF671	NM_024833.3 link	c.1208G>A	p.Gly403Glu	missense_variant	Exon 4 of 4	ENST00000317398.10	NP_079109.2	Q8TAW3
ZNF671	NM_001321376.2 link	c.977G>A	p.Gly326Glu	missense_variant	Exon 5 of 5		NP_001308305.1
ZNF671	NM_001321375.2 link	c.914G>A	p.Gly305Glu	missense_variant	Exon 3 of 3		NP_001308304.1	B7Z1N1
ZNF671	XM_017027314.2 link	c.977G>A	p.Gly326Glu	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.1208G>A	p.Gly403Glu	missense_variant	Exon 4 of 4	1	NM_024833.3	ENSP00000321848.5		Q8TAW3
ENSG00000269026	ENST00000594684.1 link	c.34-29907C>T		intron_variant	Intron 1 of 2	1		ENSP00000472160.1		M0R1X1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2132

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0491

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00345

AC:

867

AN:

251476

Hom.:

AF XY:

0.00254

AC XY:

345

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0477

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00145

AC:

2117

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

870

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0494

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000980

Gnomad4 OTH exome

AF:

0.00361

GnomAD4 genome

AF:

0.0141

AC:

2140

AN:

152230

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

976

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0492

Gnomad4 AMR

AF:

0.00432

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00205

Hom.:

Bravo

AF:

0.0165

ESP6500AA

AF:

0.0486

AC:

214

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00437

AC:

531

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-7.5

REVEL

Benign

0.065

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.13

MVP

0.58

MPC

0.75

ClinPred

0.075

GERP RS

0.81

Varity_R

0.58

gMVP

0.084

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