6-27452189-T-C

Position:

• chr6-27452189-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318891.2(ZNF184):​c.1370A>G​(p.Tyr457Cys) 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 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF184 NM_001318891.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.102

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 (HGNC:):

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=0.1590603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF184	NM_001318891.2	c.1370A>G	p.Tyr457Cys	missense_variant	6/6	ENST00000683788.1	NP_001305820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF184	ENST00000683788.1	c.1370A>G	p.Tyr457Cys	missense_variant	6/6		NM_001318891.2	ENSP00000508298.1
ZNF184	ENST00000211936.10	c.1370A>G	p.Tyr457Cys	missense_variant	6/6	1		ENSP00000211936.6
ZNF184	ENST00000377419.1	c.1370A>G	p.Tyr457Cys	missense_variant	6/6	4		ENSP00000366636.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727232

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.: 32

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

Feb 07, 2023

The c.1370A>G (p.Y457C) alteration is located in exon 6 (coding exon 5) of the ZNF184 gene. This alteration results from a A to G substitution at nucleotide position 1370, causing the tyrosine (Y) at amino acid position 457 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	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.00068	N
LIST_S2	Benign	0.79	T;.
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.47	N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.20
Sift	Benign	0.18	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.0010	B;B
Vest4		0.58
MutPred		0.30		Gain of catalytic residue at W458 (P = 0.0207);Gain of catalytic residue at W458 (P = 0.0207);
MVP		0.23
MPC		1.5
ClinPred		0.72	D
GERP RS		2.8
Varity_R		0.26
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-27419968;