19-57720878-C-T

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

3
3
12

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]

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
ZNF671NM_024833.3 linkc.1208G>A p.Gly403Glu missense_variant Exon 4 of 4 ENST00000317398.10 NP_079109.2 Q8TAW3
ZNF671NM_001321376.2 linkc.977G>A p.Gly326Glu missense_variant Exon 5 of 5 NP_001308305.1
ZNF671NM_001321375.2 linkc.914G>A p.Gly305Glu missense_variant Exon 3 of 3 NP_001308304.1 B7Z1N1
ZNF671XM_017027314.2 linkc.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
ZNF671ENST00000317398.10 linkc.1208G>A p.Gly403Glu missense_variant Exon 4 of 4 1 NM_024833.3 ENSP00000321848.5 Q8TAW3
ENSG00000269026ENST00000594684.1 linkc.34-29907C>T intron_variant Intron 1 of 2 1 ENSP00000472160.1 M0R1X1

Frequencies

GnomAD3 genomes
AF:
0.0140
AC:
2132
AN:
152112
Hom.:
49
Cov.:
33
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.:
18
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.:
50
Cov.:
35
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.:
49
Cov.:
33
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.:
14
Bravo
AF:
0.0165
ESP6500AA
AF:
0.0486
AC:
214
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00437
AC:
531
Asia WGS
AF:
0.00346
AC:
12
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
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.36
N
LIST_S2
Benign
0.52
T
MetaRNN
Benign
0.0041
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L
PrimateAI
Uncertain
0.49
T
PROVEAN
Pathogenic
-7.5
D
REVEL
Benign
0.065
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.13
MVP
0.58
MPC
0.75
ClinPred
0.075
T
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.

Other links and lift over

dbSNP: rs78797427; hg19: chr19-58232246; COSMIC: COSV58052066; COSMIC: COSV58052066; API