6-27452601-G-C

Position:

• chr6-27452601-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001318891.2(ZNF184):​c.958C>G​(p.His320Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF184 NM_001318891.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.744

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26766402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF184	NM_001318891.2	c.958C>G	p.His320Asp	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.958C>G	p.His320Asp	missense_variant	6/6		NM_001318891.2	ENSP00000508298.1
ZNF184	ENST00000211936.10	c.958C>G	p.His320Asp	missense_variant	6/6	1		ENSP00000211936.6
ZNF184	ENST00000377419.1	c.958C>G	p.His320Asp	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

Dec 06, 2024

The c.958C>G (p.H320D) 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 958, causing the histidine (H) at amino acid position 320 to be replaced by an aspartic acid (D). 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	0.97
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.093	T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.12	T;.
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.055	N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Benign	0.16
Sift	Benign	0.069	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.48	P;P
Vest4		0.55
MutPred		0.28		Loss of MoRF binding (P = 0.0849);Loss of MoRF binding (P = 0.0849);
MVP		0.26
MPC		1.5
ClinPred		0.84	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.39

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: chr6-27420380;