Genetic Variant ZNF671:p.Tyr397Tyr (chr19-57720895-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_024833.3(ZNF671):c.1191T>C(p.Tyr397Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,613,984 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0095 ( 27 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 30 hom. )

Consequence

ZNF671
NM_024833.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.462

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 (BayesDel_noAF=-0.93).

BP6

Variant 19-57720895-A-G is Benign according to our data. Variant chr19-57720895-A-G is described in ClinVar as [Benign]. Clinvar id is 790766.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 = 0.00949 (1444/152090) while in subpopulation AFR AF= 0.0332 (1379/41474). AF 95% confidence interval is 0.0318. There are 27 homozygotes in gnomad4. There are 690 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF671	NM_024833.3 link	c.1191T>C	p.Tyr397Tyr	synonymous_variant	Exon 4 of 4	ENST00000317398.10	NP_079109.2	Q8TAW3
ZNF671	NM_001321376.2 link	c.960T>C	p.Tyr320Tyr	synonymous_variant	Exon 5 of 5		NP_001308305.1
ZNF671	NM_001321375.2 link	c.897T>C	p.Tyr299Tyr	synonymous_variant	Exon 3 of 3		NP_001308304.1	B7Z1N1
ZNF671	XM_017027314.2 link	c.960T>C	p.Tyr320Tyr	synonymous_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.1191T>C	p.Tyr397Tyr	synonymous_variant	Exon 4 of 4	1	NM_024833.3	ENSP00000321848.5		Q8TAW3
ENSG00000269026	ENST00000594684.1 link	c.34-29890A>G		intron_variant	Intron 1 of 2	1		ENSP00000472160.1		M0R1X1

Frequencies

GnomAD3 genomes

AF:

0.00942

AC:

1432

AN:

151972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00269

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00268

AC:

673

AN:

251462

Hom.:

AF XY:

0.00190

AC XY:

258

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0354

Gnomad AMR exome

AF:

0.00228

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00101

AC:

1470

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000872

AC XY:

634

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0351

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00949

AC:

1444

AN:

152090

Hom.:

Cov.:

AF XY:

0.00928

AC XY:

690

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0332

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00565

Hom.:

Bravo

AF:

0.0111

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

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

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.77

DANN

Benign

0.29

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