Genetic Variant ZNF37A:p.Ser85Gly (chr10-38117404-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001324250.3(ZNF37A):c.253A>G(p.Ser85Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 1,416,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZNF37A
NM_001324250.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61

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:

PLD5P1 (HGNC:55072): (PLD5 pseudogene 1) Predicted to be involved in regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

PLD5P1 links:

ENSG00000302873 (HGNC:):

ENSG00000302873 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.085404366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF37A	NM_001324250.3 link	c.253A>G	p.Ser85Gly	missense_variant	Exon 8 of 8	ENST00000685332.1	NP_001311179.1	P17032

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF37A	ENST00000685332.1 link	c.253A>G	p.Ser85Gly	missense_variant	Exon 8 of 8		NM_001324250.3	ENSP00000508865.1		P17032
PLD5P1	ENST00000640275.1 link	n.238+2114A>G		intron_variant	Intron 7 of 17	5		ENSP00000491560.1		A0A1W2PQ67

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000184

AC:

AN:

1416384

Hom.:

Cov.:

AF XY:

0.0000199

AC XY:

AN XY:

702174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31114

American (AMR)

AF:

0.00

AC:

AN:

33824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23148

East Asian (EAS)

AF:

0.00

AC:

AN:

39412

South Asian (SAS)

AF:

0.00

AC:

AN:

77494

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51716

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5510

European-Non Finnish (NFE)

AF:

0.0000237

AC:

AN:

1095818

Other (OTH)

AF:

0.00

AC:

AN:

58348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Mar 02, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.253A>G (p.S85G) 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 253, causing the serine (S) at amino acid position 85 to be replaced by a glycine (G). 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

0.078

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.8

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0015

T;T

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.11

T;.

M_CAP

Benign

0.0014

MetaRNN

Benign

0.085

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.5

L;L

PhyloP100

2.6

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.028

Sift

Benign

0.18

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.027

B;B

Vest4

0.11

MutPred

0.28

Loss of stability (P = 0.0368);Loss of stability (P = 0.0368);

MVP

0.24

MPC

0.034

ClinPred

0.11

GERP RS

2.3

Varity_R

0.11

gMVP

0.0098

Mutation Taster

=99/1

polymorphism

(source)

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.

chr10-38117404-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over