rs193921063

Positions:

• chr6-27457372-G-T

Variant summary

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

The NM_001318891.2(ZNF184):​c.113C>A​(p.Thr38Asn) 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF184 NM_001318891.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.02

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]

(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=0.39786097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF184	NM_001318891.2	c.113C>A	p.Thr38Asn	missense_variant	4/6	ENST00000683788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF184	ENST00000683788.1	c.113C>A	p.Thr38Asn	missense_variant	4/6		NM_001318891.2	P1
ZNF184	ENST00000211936.10	c.113C>A	p.Thr38Asn	missense_variant	4/6	1		P1
	ENST00000648356.1	n.1388G>T		non_coding_transcript_exon_variant	2/2
ZNF184	ENST00000377419.1	c.113C>A	p.Thr38Asn	missense_variant	4/6	4		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.54	T;.
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	M;M
MutationTaster	Benign	0.93	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.93	P;P
Vest4		0.47
MVP		0.83
MPC		1.4
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.74
gMVP		0.52

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: rs193921063; hg19: chr6-27425151; COSMIC: COSV53005300;