rs762427265

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173658.4(ZNF660):c.494T>C(p.Ile165Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,611,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I165V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ZNF660
NM_173658.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.54

Publications

0 publications found

Variant links:

Genes affected

ZNF660 (HGNC:26720): (zinc finger protein 660) This gene encodes a protein that contains multiple C2H2 zinc finger domains, and is located in a cluster of zinc-finger encoding genes on chromosome 3. Naturally-occurring readthrough transcription is observed between this gene and the downstream zinc finger protein 197 gene and is represented by GeneID:110354863. [provided by RefSeq, May 2017]

ZNF660 links:

ZNF660-ZNF197 (HGNC:):

ZNF660-ZNF197 links:

ZNF197 (HGNC:12988): (zinc finger protein 197) This gene product belongs to the zinc finger protein superfamily, members of which are regulatory proteins characterized by nucleic acid-binding zinc finger domains. The encoded protein contains 20 tandemly arrayed C2H2-type zinc fingers, a Kruppel-associated box (KRAB) domain, and a SCAN box. This transcript turns over rapidly and contains 3' UTR AUUUA motifs, which are often a hallmark of rapid turnover. It is overexpressed in some thyroid papillary carcinomas. This gene is located in a cluster of zinc finger genes at 3p21. Naturally-occurring readthrough transcription is observed between this gene and the upstream zinc finger protein 660 gene and is represented by GeneID:110354863. [provided by RefSeq, May 2017]

ZNF197 links:

ZKSCAN7-AS1 (HGNC:53964): (ZKSCAN7 ZNF cluster antisense RNA 1)

ZKSCAN7-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075609386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF660	NM_173658.4 link	c.494T>C	p.Ile165Thr	missense_variant	Exon 3 of 3	ENST00000322734.2	NP_775929.2	Q6AZW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF660	ENST00000322734.2 link	c.494T>C	p.Ile165Thr	missense_variant	Exon 3 of 3	2	NM_173658.4	ENSP00000324605.2		Q6AZW8

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000123

AC:

AN:

251456

AF XY:

0.0000883

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000783

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150100

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40736

American (AMR)

AF:

0.000132

AC:

AN:

15130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

4990

South Asian (SAS)

AF:

0.00

AC:

AN:

4698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67384

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 26, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.494T>C (p.I165T) alteration is located in exon 3 (coding exon 1) of the ZNF660 gene. This alteration results from a T to C substitution at nucleotide position 494, causing the isoleucine (I) at amino acid position 165 to be replaced by a threonine (T). 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

0.052

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.4

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.0084

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.013

M_CAP

Benign

0.0019

MetaRNN

Benign

0.0076

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.6

PhyloP100

-2.5

PrimateAI

Benign

0.40

PROVEAN

Benign

1.6

REVEL

Benign

0.032

Sift

Benign

0.33

Sift4G

Benign

0.11

Polyphen

0.0

Vest4

0.056

MutPred

0.26

Gain of glycosylation at Y162 (P = 0.0125);

MVP

0.014

MPC

0.060

ClinPred

0.032

GERP RS

-1.6

Varity_R

0.040

gMVP

0.015

Mutation Taster

=100/0

polymorphism

(source)

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

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rs762427265

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over