chr19-12186787-G-C

Position:

• chr19-12186787-G-C

Variant summary

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

The NM_003437.5(ZNF136):​c.409G>C​(p.Glu137Gln) 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. 13/21 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: ZNF136 NM_003437.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=0.17025283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF136	NM_003437.5	c.409G>C	p.Glu137Gln	missense_variant	4/4	ENST00000343979.6
ZNF136	NM_001348014.2	c.313G>C	p.Glu105Gln	missense_variant	5/5
ZNF136	NM_001348013.2	c.211G>C	p.Glu71Gln	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF136	ENST00000343979.6	c.409G>C	p.Glu137Gln	missense_variant	4/4	1	NM_003437.5	P1
ZNF136	ENST00000464860.1	n.1573G>C		non_coding_transcript_exon_variant	3/3	1
ZNF136	ENST00000652580.1	c.313G>C	p.Glu105Gln	missense_variant	5/5
ZNF136	ENST00000439995.5	c.211G>C	p.Glu71Gln	missense_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.062	T;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.023
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.89	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.11
Sift	Benign	0.14	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.95	.;P
Vest4		0.070
MutPred		0.26		.;Loss of stability (P = 0.1562);
MVP		0.25
MPC		0.60
ClinPred		0.39	T
GERP RS		1.4
Varity_R		0.092
gMVP		0.012

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: chr19-12297602; COSMIC: COSV59711704; COSMIC: COSV59711704;