6-27452540-C-T

Position:

• chr6-27452540-C-T

Variant summary

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

The NM_001318891.2(ZNF184):​c.1019G>A​(p.Gly340Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF184 NM_001318891.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF184	NM_001318891.2	c.1019G>A	p.Gly340Glu	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.1019G>A	p.Gly340Glu	missense_variant	6/6		NM_001318891.2	ENSP00000508298.1
ZNF184	ENST00000211936.10	c.1019G>A	p.Gly340Glu	missense_variant	6/6	1		ENSP00000211936.6
ZNF184	ENST00000377419.1	c.1019G>A	p.Gly340Glu	missense_variant	6/6	4		ENSP00000366636.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Sep 01, 2021

The c.1019G>A (p.G340E) alteration is located in exon 6 (coding exon 5) of the ZNF184 gene. This alteration results from a G to A substitution at nucleotide position 1019, causing the glycine (G) at amino acid position 340 to be replaced by a glutamic acid (E). 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	0.71
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.15	T;.
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.3	D;D
REVEL	Benign	0.16
Sift	Benign	0.031	D;D
Sift4G	Uncertain	0.043	D;D
Polyphen		1.0	D;D
Vest4		0.32
MutPred		0.71		Gain of ubiquitination at K341 (P = 0.0619);Gain of ubiquitination at K341 (P = 0.0619);
MVP		0.50
MPC		1.5
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.68
gMVP		0.41

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: chr6-27420319;