rs193921014

chr19-12187261-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003437.5(ZNF136):c.883T>G(p.Leu295Val) 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 (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF136 NM_003437.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.358

Genes affected

ZNF136 (HGNC:12920): (zinc finger protein 136) This gene encodes a zinc finger protein containing a Kruppel-associated box (KRAB) A-box domain at its N-terminus, followed by fourteen contiguous C2H2 zinc finger domains and a degenerate zinc finger. The KRAB A-box showed weak transcriptional repressor activity in a reporter gene assay. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11937919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF136	NM_003437.5	c.883T>G	p.Leu295Val	missense_variant	4/4	ENST00000343979.6
ZNF136	NM_001348014.2	c.787T>G	p.Leu263Val	missense_variant	5/5
ZNF136	NM_001348013.2	c.685T>G	p.Leu229Val	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF136	ENST00000343979.6	c.883T>G	p.Leu295Val	missense_variant	4/4	1	NM_003437.5	P1
ZNF136	ENST00000464860.1	n.2047T>G		non_coding_transcript_exon_variant	3/3	1
ZNF136	ENST00000652580.1	c.787T>G	p.Leu263Val	missense_variant	5/5

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

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	0.34
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	4.9
Dann	Benign	0.78
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00012	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	2.9	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.078
Sift	Benign	0.29	T
Sift4G	Benign	0.068	T
Polyphen		0.10	B
Vest4		0.13
MutPred		0.57		Loss of stability (P = 0.0689);
MVP		0.24
MPC		0.21
ClinPred		0.12	T
GERP RS		-2.7
Varity_R		0.050
gMVP		0.027

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: rs193921014; hg19: chr19-12298076;