19-52365863-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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)
  • 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

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 Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF610	NM_001161425.2	c.485C>T	p.Ser162Leu	missense_variant	6/6	ENST00000403906.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF610	ENST00000403906.8	c.485C>T	p.Ser162Leu	missense_variant	6/6	1	NM_001161425.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250426 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135442

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Mar 14, 2023

The c.485C>T (p.S162L) alteration is located in exon 6 (coding exon 4) of the ZNF610 gene. This alteration results from a C to T substitution at nucleotide position 485, causing the serine (S) at amino acid position 162 to be replaced by a leucine (L). 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	0.099
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	15
Dann	Benign	0.89
DEOGEN2	Benign	0.051	T;T;.;T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.019	N
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.086	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.3	L;L;.;L;.;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.30	T
REVEL	Benign	0.016
Sift4G	Benign	0.10	T;T;T;T;T;T
Polyphen		0.23	B;B;B;B;B;B
Vest4		0.17
MutPred		0.31		Loss of disorder (P = 0.0118);Loss of disorder (P = 0.0118);.;Loss of disorder (P = 0.0118);.;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

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: rs1358406459; hg19: chr19-52869116; COSMIC: COSV58345057; COSMIC: COSV58345057;