3-44594731-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173658.4(ZNF660):c.538C>T(p.His180Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ZNF660
NM_173658.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF660	NM_173658.4 link	c.538C>T	p.His180Tyr	missense_variant	Exon 3 of 3	ENST00000322734.2	NP_775929.2	Q6AZW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF660	ENST00000322734.2 link	c.538C>T	p.His180Tyr	missense_variant	Exon 3 of 3	2	NM_173658.4	ENSP00000324605.2	Q6AZW8
ZNF197	ENST00000412641.1 link	c.-82+8518C>T		intron_variant	Intron 2 of 2	2		ENSP00000394713.1	C9JQH5
ZKSCAN7-AS1	ENST00000457331.2 link	n.233-37139G>A		intron_variant	Intron 2 of 2	3
ZKSCAN7-AS1	ENST00000685649.2 link	n.225-33138G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251408

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135868

show subpopulations

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000252

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000967

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 30, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.538C>T (p.H180Y) alteration is located in exon 3 (coding exon 1) of the ZNF660 gene. This alteration results from a C to T substitution at nucleotide position 538, causing the histidine (H) at amino acid position 180 to be replaced by a tyrosine (Y). 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

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.64

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-6.0

REVEL

Pathogenic

0.84

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.40

MVP

0.85

MPC

0.36

ClinPred

0.98

GERP RS

4.2

Varity_R

0.83

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over