chr6-27452129-T-C

Position:

• chr6-27452129-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001318891.2(ZNF184):​c.1430A>G​(p.Asn477Ser) 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. 15/21 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: -2.99

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034241647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF184	NM_001318891.2	c.1430A>G	p.Asn477Ser	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.1430A>G	p.Asn477Ser	missense_variant	6/6		NM_001318891.2	ENSP00000508298.1
ZNF184	ENST00000211936.10	c.1430A>G	p.Asn477Ser	missense_variant	6/6	1		ENSP00000211936.6
ZNF184	ENST00000377419.1	c.1430A>G	p.Asn477Ser	missense_variant	6/6	4		ENSP00000366636.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

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.1430A>G (p.N477S) 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 1430, causing the asparagine (N) at amino acid position 477 to be replaced by a serine (S). 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	0.066
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
DANN	Benign	0.89
DEOGEN2	Benign	0.028	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.00028	N
LIST_S2	Benign	0.078	T;.
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.034	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.054
Sift	Benign	0.53	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.0010	B;B
Vest4		0.075
MVP		0.12
MPC		0.36
ClinPred		0.068	T
GERP RS		-0.13
Varity_R		0.050
gMVP		0.047

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

LitVar

Other links and lift over

dbSNP: rs893193771; hg19: chr6-27419908;