19-57978581-C-G

Position:

• chr19-57978581-C-G

Variant summary

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

The NM_001348022.3(ZNF606):​c.2099G>C​(p.Arg700Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF606 NM_001348022.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.0570

Genes affected

ZNF606 (HGNC:25879): (zinc finger protein 606) This gene encodes a zinc finger protein containing a Kruppel-associated box (KRAB) domain at its N-terminus, followed by contiguous C2H2 zinc finger motifs. The encoded protein is a nuclear protein that can act as a transcriptional repressor of growth factor-mediated signaling pathways in a reporter gene assay. This protein has been shown to interact with the SRY-box 9 gene product, and suppresses its transcriptional activity by inhibiting its DNA binding activity. Reduced expression of this gene promotes chondrocyte differentiation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF606	NM_001348022.3	c.2099G>C	p.Arg700Thr	missense_variant	7/7	ENST00000551380.7	NP_001334951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF606	ENST00000551380.7	c.2099G>C	p.Arg700Thr	missense_variant	7/7	5	NM_001348022.3	ENSP00000446972.2
ZNF606	ENST00000341164.9	c.2099G>C	p.Arg700Thr	missense_variant	7/7	1		ENSP00000343617.4
ZNF606	ENST00000550599.6	n.*1833G>C		non_coding_transcript_exon_variant	6/6	2		ENSP00000446845.1
ZNF606	ENST00000550599.6	n.*1833G>C		3_prime_UTR_variant	6/6	2		ENSP00000446845.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Richard Lifton Laboratory, Yale University School of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0039	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.9	L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.18
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.64		Loss of phosphorylation at T703 (P = 0.0692);
MVP		0.50
MPC		0.92
ClinPred		0.97	D
GERP RS		4.4
Varity_R		0.31
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

LitVar

Other links and lift over

dbSNP: rs386352385; hg19: chr19-58489949;