6-27451659-T-G

Variant summary

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

The NM_001318891.2(ZNF184):c.1900A>C(p.Lys634Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: ZNF184 NM_001318891.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0750

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]

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=0.11020529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF184	NM_001318891.2	c.1900A>C	p.Lys634Gln	missense_variant	6/6	ENST00000683788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF184	ENST00000683788.1	c.1900A>C	p.Lys634Gln	missense_variant	6/6		NM_001318891.2	P1
ZNF184	ENST00000211936.10	c.1900A>C	p.Lys634Gln	missense_variant	6/6	1		P1
ZNF184	ENST00000377419.1	c.1900A>C	p.Lys634Gln	missense_variant	6/6	4		P1

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

Oct 02, 2023

The c.1900A>C (p.K634Q) alteration is located in exon 6 (coding exon 5) of the ZNF184 gene. This alteration results from a A to C substitution at nucleotide position 1900, causing the lysine (K) at amino acid position 634 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	0.28
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.035	T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.21	T;.
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.83	L;L
MutationTaster	Benign	0.93	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.012	D;D
Sift4G	Benign	0.063	T;T
Polyphen		0.26	B;B
Vest4		0.30
MutPred		0.51		Loss of methylation at K634 (P = 0.01);Loss of methylation at K634 (P = 0.01);
MVP		0.31
MPC		1.4
ClinPred		0.68	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.14

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: chr6-27419438;