Variant chr19-12185800-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003437.5(ZNF136):c.19G>A(p.Glu7Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ZNF136
NM_003437.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.945

Variant links:

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]

ZNF136 links:

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ACMG classification

Classification made for transcript

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=0.38564414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF136	NM_003437.5 linkuse as main transcript	c.19G>A	p.Glu7Lys	missense_variant	2/4	ENST00000343979.6
ZNF136	NM_001348014.2 linkuse as main transcript	c.-78G>A		5_prime_UTR_variant	3/5
ZNF136	NM_001348013.2 linkuse as main transcript	c.-68-314G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF136	ENST00000343979.6 linkuse as main transcript	c.19G>A	p.Glu7Lys	missense_variant	2/4	1	NM_003437.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 09, 2023

The c.19G>A (p.E7K) alteration is located in exon 2 (coding exon 2) of the ZNF136 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the glutamic acid (E) at amino acid position 7 to be replaced by a lysine (K). 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

0.21

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

0.046

Eigen_PC

Benign

-0.097

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.69

M_CAP

Benign

0.0031

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.17

Sift

Benign

0.056

Sift4G

Benign

0.54

Polyphen

1.0

Vest4

0.43

MutPred

0.60

Gain of methylation at E7 (P = 0.0037);

MVP

0.28

MPC

0.77

ClinPred

0.94

GERP RS

1.2

Varity_R

0.20

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over