Variant 19-32352978-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001136156.2(ZNF507):c.148A>G(p.Lys50Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF507
NM_001136156.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.41

Variant links:

Genes affected

ZNF507 (HGNC:23783): (zinc finger protein 507) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF507 links:

ZNF507 (HGNC:):

ZNF507 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
ZNF507	NM_001136156.2 linkuse as main transcript	c.148A>G	p.Lys50Glu	missense_variant	3/7	ENST00000355898.6	NP_001129628.1	Q8TCN5-1
ZNF507	NM_014910.5 linkuse as main transcript	c.148A>G	p.Lys50Glu	missense_variant	2/6		NP_055725.2	Q8TCN5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF507	ENST00000355898.6 linkuse as main transcript	c.148A>G	p.Lys50Glu	missense_variant	3/7	1	NM_001136156.2	ENSP00000348162.4	Q8TCN5-1
ZNF507	ENST00000544431.5 linkuse as main transcript	c.148A>G	p.Lys50Glu	missense_variant	3/8	1		ENSP00000441549.1	B9EGE7
ZNF507	ENST00000311921.8 linkuse as main transcript	c.148A>G	p.Lys50Glu	missense_variant	2/6	1		ENSP00000312277.2	Q8TCN5-1
ZNF507	ENST00000587084.5 linkuse as main transcript	n.403A>G		non_coding_transcript_exon_variant	3/4	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727134

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:

0.00

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

Jan 27, 2022

The c.148A>G (p.K50E) alteration is located in exon 3 (coding exon 1) of the ZNF507 gene. This alteration results from a A to G substitution at nucleotide position 148, causing the lysine (K) at amino acid position 50 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

0.95

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;D;D

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;M

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.3

N;N;N

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.71

MutPred

0.33

Loss of methylation at K50 (P = 0.0032);Loss of methylation at K50 (P = 0.0032);Loss of methylation at K50 (P = 0.0032);

MVP

0.30

MPC

0.37

ClinPred

0.94

GERP RS

5.5

Varity_R

0.63

gMVP

0.48

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