rs149563831

Variant names:

• chr19-57720897-A-G
• rs149563831
• NM_024833.3:c.1189T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024833.3(ZNF671):​c.1189T>C​(p.Tyr397His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Y397Y) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: ZNF671 NM_024833.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76
• Publications: 2 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15031463).

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.1189T>C	p.Tyr397His	missense	Exon 4 of 4	NP_079109.2	Q8TAW3
	ZNF671	NM_001321376.2		c.958T>C	p.Tyr320His	missense	Exon 5 of 5	NP_001308305.1
	ZNF671	NM_001321375.2		c.895T>C	p.Tyr299His	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.1189T>C	p.Tyr397His	missense	Exon 4 of 4	ENSP00000321848.5	Q8TAW3
	ENSG00000269026	ENST00000594684.1	TSL:1	c.34-29888A>G		intron	N/A	ENSP00000472160.1	M0R1X1
	ZNF671	ENST00000925804.1		c.1351T>C	p.Tyr451His	missense	Exon 4 of 4	ENSP00000595864.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152008 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.000279

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000135 AC: 34 AN: 251456 AF XY: 0.000162

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000175 AC: 256 AN: 1461894 Hom.: 0 Cov.: 35 AF XY: 0.000184 AC XY: 134 AN XY: 727248

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

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

European-Non Finnish (NFE) AF: 0.000218 AC: 242 AN: 1112012

Other (OTH) AF: 0.0000662 AC: 4 AN: 60396

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152126 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41496

American (AMR) AF: 0.00 AC: 0 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

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

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000286 Hom.: 1

Bravo AF: 0.000178

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000157 AC: 19

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000296

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	Pathogenic	0.68
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.8
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.047
Sift	Benign	0.067	T
Sift4G	Uncertain	0.024	D
Polyphen		0.90	P
Vest4		0.22
MVP		0.37
MPC		0.72
ClinPred		0.77	D
GERP RS		1.9
Varity_R		0.30
gMVP		0.18
Mutation Taster		=97/3	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: rs149563831; hg19: chr19-58232265;