Variant 10-38118203-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001324250.3(ZNF37A):c.1052G>A(p.Gly351Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,988 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

ZNF37A
NM_001324250.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00783512).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF37A	NM_001324250.3 linkuse as main transcript	c.1052G>A	p.Gly351Glu	missense_variant	8/8	ENST00000685332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF37A	ENST00000685332.1 linkuse as main transcript	c.1052G>A	p.Gly351Glu	missense_variant	8/8		NM_001324250.3	P1
ZNF37A	ENST00000351773.7 linkuse as main transcript	c.1052G>A	p.Gly351Glu	missense_variant	8/8	1		P1
ZNF37A	ENST00000361085.9 linkuse as main transcript	c.1052G>A	p.Gly351Glu	missense_variant	7/7	2		P1
ZNF37A	ENST00000638053.1 linkuse as main transcript	c.238+2913G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000920

AC:

140

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00133

AC:

334

AN:

250848

Hom.:

AF XY:

0.00132

AC XY:

179

AN XY:

135574

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00557

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00287

Gnomad NFE exome

AF:

0.00165

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.00124

AC:

1812

AN:

1461728

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

915

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00586

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.00292

Gnomad4 NFE exome

AF:

0.00123

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.000919

AC:

140

AN:

152260

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.000892

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00122

AC:

148

EpiCase

AF:

0.000982

EpiControl

AF:

0.00130

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

Jan 03, 2024

The c.1052G>A (p.G351E) 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 1052, causing the glycine (G) at amino acid position 351 to be replaced by a glutamic acid (E). 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

Pathogenic

0.89

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

0.0081

Eigen_PC

Benign

-0.023

FATHMM_MKL

Benign

0.00068

LIST_S2

Benign

0.12

T;.

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0078

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

0.92

N;N

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-6.6

D;D

REVEL

Benign

0.062

Sift

Benign

0.046

D;D

Sift4G

Uncertain

0.040

D;D

Polyphen

0.82

P;P

Vest4

0.11

MVP

0.42

MPC

0.27

ClinPred

0.075

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.016

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