19-52365863-C-T

Variant names:

• chr19-52365863-C-T
• rs1358406459
• NM_001161425.2:c.485C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001161425.2(ZNF610):​c.485C>T​(p.Ser162Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF610 NM_001161425.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.167
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0862008).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161425.2. 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
	ZNF610	NM_001161425.2	MANE Select	c.485C>T	p.Ser162Leu	missense	Exon 6 of 6	NP_001154897.1	Q8N9Z0-1
	ZNF610	NM_001161426.2		c.485C>T	p.Ser162Leu	missense	Exon 6 of 6	NP_001154898.1	Q8N9Z0-1
	ZNF610	NM_173530.3		c.485C>T	p.Ser162Leu	missense	Exon 6 of 6	NP_775801.2	Q8N9Z0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF610	ENST00000403906.8	TSL:1 MANE Select	c.485C>T	p.Ser162Leu	missense	Exon 6 of 6	ENSP00000383922.2	Q8N9Z0-1
	ZNF610	ENST00000321287.12	TSL:1	c.485C>T	p.Ser162Leu	missense	Exon 6 of 6	ENSP00000324441.8	Q8N9Z0-1
	ZNF610	ENST00000601151.5	TSL:1	c.356C>T	p.Ser119Leu	missense	Exon 5 of 5	ENSP00000471021.1	Q8N9Z0-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250426 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461174 Hom.: 0 Cov.: 56 AF XY: 0.00 AC XY: 0 AN XY: 726860

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 85934

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 33

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	Benign	0.099
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.051	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.052	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.17
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.016
Sift	Benign	0.090	T
Sift4G	Benign	0.10	T
Polyphen		0.23	B
Vest4		0.17
MutPred		0.31		Loss of disorder (P = 0.0118)
MVP		0.17
MPC		0.13
ClinPred		0.070	T
GERP RS		-1.9
Varity_R		0.11
gMVP		0.067
Mutation Taster		=98/2	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: rs1358406459; hg19: chr19-52869116; COSMIC: COSV58345057; COSMIC: COSV58345057;