Variant 10-38117434-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001324250.3(ZNF37A):c.283G>A(p.Glu95Lys) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF37A
NM_001324250.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.955

Variant links:

Genes affected

ZNF37A (HGNC:13102): (zinc finger protein 37A) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF37A links:

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ACMG classification

Classification made for transcript

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=0.08961436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF37A	NM_001324250.3 linkuse as main transcript	c.283G>A	p.Glu95Lys	missense_variant	8/8	ENST00000685332.1	NP_001311179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF37A	ENST00000685332.1 linkuse as main transcript	c.283G>A	p.Glu95Lys	missense_variant	8/8		NM_001324250.3	ENSP00000508865	P1
ZNF37A	ENST00000351773.7 linkuse as main transcript	c.283G>A	p.Glu95Lys	missense_variant	8/8	1		ENSP00000329141	P1
ZNF37A	ENST00000361085.9 linkuse as main transcript	c.283G>A	p.Glu95Lys	missense_variant	7/7	2		ENSP00000354377	P1
ZNF37A	ENST00000638053.1 linkuse as main transcript	c.238+2144G>A		intron_variant		5		ENSP00000490669

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000432

AC:

AN:

231678

Hom.:

AF XY:

0.00

AC XY:

AN XY:

125384

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000925

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Oct 12, 2022

The c.283G>A (p.E95K) alteration is located in exon 8 (coding exon 4) of the ZNF37A gene. This alteration results from a G to A substitution at nucleotide position 283, causing the glutamic acid (E) at amino acid position 95 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

0.080

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.0

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0066

T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.00031

LIST_S2

Benign

0.62

T;.

M_CAP

Benign

0.0017

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.044

Sift

Benign

0.18

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.012

B;B

Vest4

0.14

MutPred

0.35

Gain of methylation at E95 (P = 0.0016);Gain of methylation at E95 (P = 0.0016);

MVP

0.22

MPC

0.036

ClinPred

0.081

GERP RS

2.2

Varity_R

0.081

gMVP

0.067

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

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