Variant 16-31076578-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014699.4(ZNF646):c.254C>G(p.Ser85Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,334 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: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ZNF646
NM_014699.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21

Variant links:

Genes affected

ZNF646 (HGNC:29004): (zinc finger protein 646) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF646 links:

ZNF646 (HGNC:):

ZNF646 links:

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ACMG classification

Classification made for transcript

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=0.25764522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF646	NM_014699.4 linkuse as main transcript	c.254C>G	p.Ser85Cys	missense_variant	2/3	ENST00000300850.5	NP_055514.3	O15015-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF646	ENST00000300850.5 linkuse as main transcript	c.254C>G	p.Ser85Cys	missense_variant	2/3	1	NM_014699.4	ENSP00000300850.5	O15015-2
ZNF646	ENST00000394979.2 linkuse as main transcript	c.254C>G	p.Ser85Cys	missense_variant	1/1	6		ENSP00000378429.2	O15015-1
ZNF646	ENST00000428260.1 linkuse as main transcript	c.254C>G	p.Ser85Cys	missense_variant	2/2	3		ENSP00000391271.1	C9J3L0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250764

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135666

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:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460334

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726220

show subpopulations

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.254C>G (p.S85C) alteration is located in exon 2 (coding exon 1) of the ZNF646 gene. This alteration results from a C to G substitution at nucleotide position 254, causing the serine (S) at amino acid position 85 to be replaced by a cysteine (C). 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

0.17

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.058

.;T;T

Eigen

Benign

-0.031

Eigen_PC

Benign

-0.076

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.10

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.7

L;.;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.5

N;D;N

REVEL

Benign

0.17

Sift

Benign

0.051

T;D;T

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.97

D;.;.

Vest4

0.12

MutPred

0.48

Loss of MoRF binding (P = 0.0787);Loss of MoRF binding (P = 0.0787);Loss of MoRF binding (P = 0.0787);

MVP

0.64

MPC

0.25

ClinPred

0.26

GERP RS

4.0

Varity_R

0.072

gMVP

0.24

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