19-52365769-G-T

Variant names:

• chr19-52365769-G-T
• rs2241586
• NM_001161425.2:c.391G>T

Variant summary

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

The NM_001161425.2(ZNF610):​c.391G>T​(p.Ala131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 1,613,880 control chromosomes in the GnomAD database, including 605,768 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.86 (55943 hom., cov: 32)
  • Exomes 𝑓: 0.87 (549825 hom.)
• Consequence: ZNF610 NM_001161425.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 29 publications found

Genes affected

ZNF610 (HGNC:26687): (zinc finger protein 610) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific 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 active 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=1.1387762E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF610	NM_001161425.2	c.391G>T	p.Ala131Ser	missense_variant	Exon 6 of 6	ENST00000403906.8	NP_001154897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF610	ENST00000403906.8	c.391G>T	p.Ala131Ser	missense_variant	Exon 6 of 6	1	NM_001161425.2	ENSP00000383922.2

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130228 AN: 152044 Hom.: 55908 Cov.: 32

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.899

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.874

GnomAD2 exomes AF: 0.839 AC: 210815 AN: 251244 AF XY: 0.849

Gnomad AFR exome AF: 0.848

Gnomad AMR exome AF: 0.730

Gnomad ASJ exome AF: 0.885

Gnomad EAS exome AF: 0.611

Gnomad FIN exome AF: 0.872

Gnomad NFE exome AF: 0.880

Gnomad OTH exome AF: 0.861

GnomAD4 exome AF: 0.866 AC: 1265229 AN: 1461718 Hom.: 549825 Cov.: 60 AF XY: 0.868 AC XY: 630879 AN XY: 727150

African (AFR) AF: 0.848 AC: 28403 AN: 33476

American (AMR) AF: 0.737 AC: 32939 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 23132 AN: 26132

East Asian (EAS) AF: 0.621 AC: 24653 AN: 39694

South Asian (SAS) AF: 0.903 AC: 77848 AN: 86212

European-Finnish (FIN) AF: 0.875 AC: 46746 AN: 53420

Middle Eastern (MID) AF: 0.883 AC: 5087 AN: 5762

European-Non Finnish (NFE) AF: 0.876 AC: 974109 AN: 1111940

Other (OTH) AF: 0.866 AC: 52312 AN: 60388

GnomAD4 genome AF: 0.856 AC: 130311 AN: 152162 Hom.: 55943 Cov.: 32 AF XY: 0.856 AC XY: 63655 AN XY: 74384

African (AFR) AF: 0.852 AC: 35383 AN: 41524

American (AMR) AF: 0.805 AC: 12295 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 3034 AN: 3470

East Asian (EAS) AF: 0.625 AC: 3226 AN: 5160

South Asian (SAS) AF: 0.898 AC: 4328 AN: 4818

European-Finnish (FIN) AF: 0.877 AC: 9285 AN: 10592

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.880 AC: 59864 AN: 68004

Other (OTH) AF: 0.871 AC: 1838 AN: 2110

Alfa AF: 0.866 Hom.: 232834

Bravo AF: 0.846

TwinsUK AF: 0.869 AC: 3221

ALSPAC AF: 0.874 AC: 3368

ESP6500AA AF: 0.846 AC: 3729

ESP6500EA AF: 0.876 AC: 7532

ExAC AF: 0.848 AC: 102897

Asia WGS AF: 0.766 AC: 2665 AN: 3478

EpiCase AF: 0.881

EpiControl AF: 0.884

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.019
DANN	Benign	0.12
DEOGEN2	Benign	0.0015	T;T;.;T;.;T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.00070	N
LIST_S2	Benign	0.031	.;.;.;.;T;T
MetaRNN	Benign	0.0000011	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.1	N;N;.;N;.;N
PhyloP100		-1.5
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.3	.;N;.;N;.;.
REVEL	Benign	0.010
Sift	Benign	1.0	.;T;.;T;.;.
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;B
Vest4		0.0090
MPC		0.13
ClinPred		0.000016	T
GERP RS		-2.2
Varity_R		0.035
gMVP		0.065
Mutation Taster		=100/0	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: rs2241586; hg19: chr19-52869022; COSMIC: COSV58343648; COSMIC: COSV58343648;