Variant 10-38117573-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001324250.3(ZNF37A):c.422A>G(p.Asn141Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

ZNF37A
NM_001324250.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.70

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01518029).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF37A	NM_001324250.3 linkuse as main transcript	c.422A>G	p.Asn141Ser	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.422A>G	p.Asn141Ser	missense_variant	8/8		NM_001324250.3	P1
ZNF37A	ENST00000351773.7 linkuse as main transcript	c.422A>G	p.Asn141Ser	missense_variant	8/8	1		P1
ZNF37A	ENST00000361085.9 linkuse as main transcript	c.422A>G	p.Asn141Ser	missense_variant	7/7	2		P1
ZNF37A	ENST00000638053.1 linkuse as main transcript	c.238+2283A>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249560

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

134988

show subpopulations

Gnomad AFR exome

AF:

0.000438

Gnomad AMR exome

AF:

0.0000291

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461092

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726792

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000853

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000330

AC:

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

Sep 20, 2023

The c.422A>G (p.N141S) alteration is located in exon 8 (coding exon 4) of the ZNF37A gene. This alteration results from a A to G substitution at nucleotide position 422, causing the asparagine (N) at amino acid position 141 to be replaced by a serine (S). 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

0.088

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.42

DANN

Benign

0.57

DEOGEN2

Benign

0.00065

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.000010

LIST_S2

Benign

0.083

T;.

M_CAP

Benign

0.00073

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.2

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.59

N;N

REVEL

Benign

0.012

Sift

Benign

0.50

T;T

Sift4G

Benign

0.070

T;T

Polyphen

0.010

B;B

Vest4

0.038

MVP

0.12

MPC

0.028

ClinPred

0.021

GERP RS

-3.9

Varity_R

0.010

gMVP

0.0093

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