19-57720633-C-T

Variant names:

• chr19-57720633-C-T
• rs200134520
• NM_024833.3:c.1453G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_024833.3(ZNF671):​c.1453G>A​(p.Gly485Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,614,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ZNF671 NM_024833.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50
• Publications: 0 publications found

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]

ENSG00000269026 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34522286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024833.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF671	NM_024833.3	MANE Select	c.1453G>A	p.Gly485Arg	missense	Exon 4 of 4	NP_079109.2	Q8TAW3
	ZNF671	NM_001321376.2		c.1222G>A	p.Gly408Arg	missense	Exon 5 of 5	NP_001308305.1
	ZNF671	NM_001321375.2		c.1159G>A	p.Gly387Arg	missense	Exon 3 of 3	NP_001308304.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF671	ENST00000317398.10	TSL:1 MANE Select	c.1453G>A	p.Gly485Arg	missense	Exon 4 of 4	ENSP00000321848.5	Q8TAW3
	ENSG00000269026	ENST00000594684.1	TSL:1	c.34-30152C>T		intron	N/A	ENSP00000472160.1	M0R1X1
	ZNF671	ENST00000925804.1		c.1615G>A	p.Gly539Arg	missense	Exon 4 of 4	ENSP00000595864.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

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

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251490 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1461894 Hom.: 0 Cov.: 35 AF XY: 0.0000165 AC XY: 12 AN XY: 727248

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152290 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74466

African (AFR) AF: 0.0000481 AC: 2 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.042
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.5
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Benign	0.12
Sift	Benign	0.039	D
Sift4G	Uncertain	0.039	D
Polyphen		1.0	D
Vest4		0.21
MutPred		0.67		Loss of ubiquitination at K483 (P = 0.0271)
MVP		0.63
MPC		0.72
ClinPred		0.83	D
GERP RS		1.9
Varity_R		0.23
gMVP		0.11
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs200134520; hg19: chr19-58232001;