6-27451411-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001318891.2(ZNF184):​c.2148C>G​(p.His716Gln) 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 pathogenic 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

Scores

7
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.814
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.806

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF184NM_001318891.2 linkc.2148C>G p.His716Gln missense_variant 6/6 ENST00000683788.1 NP_001305820.1 Q99676A0A024RCM2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF184ENST00000683788.1 linkc.2148C>G p.His716Gln missense_variant 6/6 NM_001318891.2 ENSP00000508298.1 Q99676
ZNF184ENST00000211936.10 linkc.2148C>G p.His716Gln missense_variant 6/61 ENSP00000211936.6 Q99676
ZNF184ENST00000377419.1 linkc.2148C>G p.His716Gln missense_variant 6/64 ENSP00000366636.1 Q99676

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 22, 2023The c.2148C>G (p.H716Q) alteration is located in exon 6 (coding exon 5) of the ZNF184 gene. This alteration results from a C to G substitution at nucleotide position 2148, causing the histidine (H) at amino acid position 716 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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Uncertain
0.42
T;T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.0021
N
LIST_S2
Benign
0.79
T;.
M_CAP
Uncertain
0.26
D
MetaRNN
Pathogenic
0.81
D;D
MetaSVM
Uncertain
0.19
D
MutationAssessor
Pathogenic
3.6
H;H
PrimateAI
Uncertain
0.79
T
PROVEAN
Pathogenic
-6.0
D;D
REVEL
Uncertain
0.55
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.37
MutPred
0.80
Gain of disorder (P = 0.1117);Gain of disorder (P = 0.1117);
MVP
0.72
MPC
0.47
ClinPred
0.99
D
GERP RS
-3.1
Varity_R
0.81
gMVP
0.38

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: chr6-27419190; API