rs2921563

Variant names:

• chr19-37363138-G-A
• rs2921563
• NM_001353803.2:c.1286G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-37363138-G-A
• chr19-37363138-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001353803.2(ZNF875):​c.1286G>A​(p.Arg429His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 1,613,674 control chromosomes in the GnomAD database, including 2,480 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.080 (736 hom., cov: 33)
  • Exomes 𝑓: 0.042 (1744 hom.)
• Consequence: ZNF875 NM_001353803.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333
• Publications: 18 publications found

Genes affected

ZNF875 (HGNC:4928): (zinc finger protein 875) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014192164).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF875	NM_001353803.2	c.1286G>A	p.Arg429His	missense_variant	Exon 5 of 5	ENST00000392153.8	NP_001340732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF875	ENST00000392153.8	c.1286G>A	p.Arg429His	missense_variant	Exon 5 of 5	1	NM_001353803.2	ENSP00000375994.3

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 12151 AN: 151692 Hom.: 735 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.0827

Gnomad SAS AF: 0.0212

Gnomad FIN AF: 0.0618

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.0342

Gnomad OTH AF: 0.0697

GnomAD2 exomes AF: 0.0539 AC: 13547 AN: 251320 AF XY: 0.0487

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.0739

Gnomad ASJ exome AF: 0.0375

Gnomad EAS exome AF: 0.0884

Gnomad FIN exome AF: 0.0593

Gnomad NFE exome AF: 0.0341

Gnomad OTH exome AF: 0.0516

GnomAD4 exome AF: 0.0417 AC: 60891 AN: 1461864 Hom.: 1744 Cov.: 33 AF XY: 0.0407 AC XY: 29614 AN XY: 727228

African (AFR) AF: 0.173 AC: 5807 AN: 33476

American (AMR) AF: 0.0764 AC: 3418 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0368 AC: 961 AN: 26134

East Asian (EAS) AF: 0.0822 AC: 3262 AN: 39700

South Asian (SAS) AF: 0.0225 AC: 1939 AN: 86258

European-Finnish (FIN) AF: 0.0610 AC: 3259 AN: 53416

Middle Eastern (MID) AF: 0.0213 AC: 123 AN: 5768

European-Non Finnish (NFE) AF: 0.0350 AC: 38907 AN: 1111996

Other (OTH) AF: 0.0532 AC: 3215 AN: 60394

GnomAD4 genome AF: 0.0801 AC: 12157 AN: 151810 Hom.: 736 Cov.: 33 AF XY: 0.0795 AC XY: 5901 AN XY: 74194

African (AFR) AF: 0.172 AC: 7096 AN: 41346

American (AMR) AF: 0.0853 AC: 1303 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3470

East Asian (EAS) AF: 0.0825 AC: 422 AN: 5114

South Asian (SAS) AF: 0.0206 AC: 99 AN: 4816

European-Finnish (FIN) AF: 0.0618 AC: 652 AN: 10546

Middle Eastern (MID) AF: 0.0241 AC: 7 AN: 290

European-Non Finnish (NFE) AF: 0.0342 AC: 2324 AN: 67936

Other (OTH) AF: 0.0699 AC: 147 AN: 2102

Alfa AF: 0.0469 Hom.: 1124

Bravo AF: 0.0873

TwinsUK AF: 0.0307 AC: 114

ALSPAC AF: 0.0348 AC: 134

ESP6500AA AF: 0.165 AC: 725

ESP6500EA AF: 0.0337 AC: 290

ExAC AF: 0.0539 AC: 6539

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;.;.;.;T;T
Eigen	Benign	0.052
Eigen_PC	Benign	-0.068
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.37	.;T;T;T;T;T
MetaRNN	Benign	0.0014	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;.;.;.;L;.
PhyloP100		-0.33
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.4	.;D;D;.;D;D
REVEL	Benign	0.11
Sift	Benign	0.12	.;T;T;.;T;T
Sift4G	Uncertain	0.038	D;D;T;T;T;T
Polyphen		0.99, 1.0, 1.0	.;.;D;.;D;D
Vest4		0.16
MPC		0.094
ClinPred		0.040	T
GERP RS		0.79
Varity_R		0.086
gMVP		0.072
Mutation Taster		=94/6	polymorphism (auto)

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: rs2921563; hg19: chr19-37854040; COSMIC: COSV60990235; COSMIC: COSV60990235;