Variant 10-38114876-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001324250.3(ZNF37A):c.137C>T(p.Ser46Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,468 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZNF37A
NM_001324250.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.991

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:

ZNF37A (HGNC:):

ZNF37A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF37A	NM_001324250.3 linkuse as main transcript	c.137C>T	p.Ser46Leu	missense_variant	6/8	ENST00000685332.1	NP_001311179.1	P17032

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF37A	ENST00000685332.1 linkuse as main transcript	c.137C>T	p.Ser46Leu	missense_variant	6/8		NM_001324250.3	ENSP00000508865.1		P17032
PLD5P1	ENST00000640275.1 linkuse as main transcript	n.137C>T		non_coding_transcript_exon_variant	6/18	5		ENSP00000491560.1		A0A1W2PQ67

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458468

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725296

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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 28, 2024

The c.137C>T (p.S46L) alteration is located in exon 6 (coding exon 2) of the ZNF37A gene. This alteration results from a C to T substitution at nucleotide position 137, causing the serine (S) at amino acid position 46 to be replaced by a leucine (L). 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

-0.054

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.75

T;T;.

M_CAP

Benign

0.0024

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-0.99

MutationAssessor

Pathogenic

3.2

.;M;M

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-4.8

.;D;D

REVEL

Benign

0.092

Sift

Uncertain

0.0020

.;D;D

Sift4G

Uncertain

0.011

.;D;D

Polyphen

0.87

.;P;P

Vest4

0.63, 0.63

MutPred

0.82

Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);

MVP

0.30

MPC

0.22

ClinPred

0.95

GERP RS

1.6

Varity_R

0.35

gMVP

0.075

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over