19-52366160-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001161425.2(ZNF610):c.782A>G(p.Lys261Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF610 NM_001161425.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.29

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04053828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF610	NM_001161425.2	c.782A>G	p.Lys261Arg	missense_variant	6/6	ENST00000403906.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF610	ENST00000403906.8	c.782A>G	p.Lys261Arg	missense_variant	6/6	1	NM_001161425.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2022

The c.782A>G (p.K261R) alteration is located in exon 6 (coding exon 4) of the ZNF610 gene. This alteration results from a A to G substitution at nucleotide position 782, causing the lysine (K) at amino acid position 261 to be replaced by an arginine (R). 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	Benign	0.098
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	13
Dann	Uncertain	0.99
DEOGEN2	Benign	0.045	T;T;.;T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.024	N
M_CAP	Benign	0.00074	T
MetaRNN	Benign	0.041	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N;N;.;N;.;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
REVEL	Benign	0.0060
Sift4G	Uncertain	0.045	D;D;D;D;D;D
Polyphen		0.044	B;B;B;B;B;B
Vest4		0.043
MutPred		0.35		Loss of methylation at K261 (P = 6e-04);Loss of methylation at K261 (P = 6e-04);.;Loss of methylation at K261 (P = 6e-04);.;Loss of methylation at K261 (P = 6e-04);
MVP		0.12
MPC		0.19
ClinPred		0.044	T
GERP RS		0.73
Varity_R		0.078
gMVP		0.015

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

Other links and lift over

dbSNP: rs1307637272; hg19: chr19-52869413;