Variant 6-27453243-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001318891.2(ZNF184):c.316G>C(p.Glu106Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,596,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ZNF184
NM_001318891.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.286

Variant links:

Genes affected

ZNF184 (HGNC:12975): (zinc finger protein 184) The protein encoded by this gene is predicted to be a Kruppel C2H2-type zinc-finger protein family member. Sequence analysis predicts that the protein contains two Kruppel associated box (KRAB) boxes in the N-terminus and highly conserved zinc finger motifs at the C-terminus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2016]

ZNF184 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0135943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF184	NM_001318891.2 linkuse as main transcript	c.316G>C	p.Glu106Gln	missense_variant	6/6	ENST00000683788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF184	ENST00000683788.1 linkuse as main transcript	c.316G>C	p.Glu106Gln	missense_variant	6/6		NM_001318891.2	P1
ZNF184	ENST00000211936.10 linkuse as main transcript	c.316G>C	p.Glu106Gln	missense_variant	6/6	1		P1
ZNF184	ENST00000377419.1 linkuse as main transcript	c.316G>C	p.Glu106Gln	missense_variant	6/6	4		P1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000103

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000103

AC:

AN:

232026

Hom.:

AF XY:

0.0000954

AC XY:

AN XY:

125756

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.000133

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:

0.0000279

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000360

AC:

AN:

1443890

Hom.:

Cov.:

AF XY:

0.0000348

AC XY:

AN XY:

717444

show subpopulations

Gnomad4 AFR exome

AF:

0.00121

Gnomad4 AMR exome

AF:

0.0000991

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:

0.00000452

Gnomad4 OTH exome

AF:

0.0000504

GnomAD4 genome

AF:

0.000282

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.000344

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

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

Jan 16, 2024

The c.316G>C (p.E106Q) alteration is located in exon 6 (coding exon 5) of the ZNF184 gene. This alteration results from a G to C substitution at nucleotide position 316, causing the glutamic acid (E) at amino acid position 106 to be replaced by a glutamine (Q). 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

0.082

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.71

Cadd

Benign

Dann

Benign

0.75

DEOGEN2

Benign

0.037

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.17

T;.

M_CAP

Benign

0.0030

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.0070

Sift

Benign

0.15

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.010

B;B

Vest4

0.17

MVP

0.21

MPC

0.68

ClinPred

0.0031

GERP RS

2.5

Varity_R

0.062

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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