chr19-57721142-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024833.3(ZNF671):​c.944G>A​(p.Cys315Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,182 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ZNF671
NM_024833.3 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF671NM_024833.3 linkc.944G>A p.Cys315Tyr missense_variant Exon 4 of 4 ENST00000317398.10 NP_079109.2 Q8TAW3
ZNF671NM_001321376.2 linkc.713G>A p.Cys238Tyr missense_variant Exon 5 of 5 NP_001308305.1
ZNF671NM_001321375.2 linkc.650G>A p.Cys217Tyr missense_variant Exon 3 of 3 NP_001308304.1 B7Z1N1
ZNF671XM_017027314.2 linkc.713G>A p.Cys238Tyr 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.944G>A p.Cys315Tyr missense_variant Exon 4 of 4 1 NM_024833.3 ENSP00000321848.5 Q8TAW3
ENSG00000269026ENST00000594684.1 linkc.34-29643C>T intron_variant Intron 1 of 2 1 ENSP00000472160.1 M0R1X1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152206
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00000398
AC:
1
AN:
251444
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
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:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461858
Hom.:
0
Cov.:
35
AF XY:
0.00000413
AC XY:
3
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152324
Hom.:
0
Cov.:
33
AF XY:
0.0000268
AC XY:
2
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.00
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:
0.000106
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 02, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.944G>A (p.C315Y) 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 944, causing the cysteine (C) at amino acid position 315 to be replaced by a tyrosine (Y). 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
Pathogenic
0.91
BayesDel_addAF
Benign
-0.00034
T
BayesDel_noAF
Uncertain
-0.060
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.44
T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.37
T
M_CAP
Benign
0.045
D
MetaRNN
Uncertain
0.53
D
MetaSVM
Uncertain
0.017
D
MutationAssessor
Pathogenic
3.3
M
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-10
D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.29
MVP
0.85
MPC
0.87
ClinPred
1.0
D
GERP RS
1.9
Varity_R
0.76
gMVP
0.37

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: rs567600305; hg19: chr19-58232510; API