19-32352841-G-A

Position:

• chr19-32352841-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136156.2(ZNF507):​c.11G>A​(p.Ser4Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF507 NM_001136156.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118652076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF507	NM_001136156.2	c.11G>A	p.Ser4Asn	missense_variant	3/7	ENST00000355898.6	NP_001129628.1
ZNF507	NM_014910.5	c.11G>A	p.Ser4Asn	missense_variant	2/6		NP_055725.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF507	ENST00000355898.6	c.11G>A	p.Ser4Asn	missense_variant	3/7	1	NM_001136156.2	ENSP00000348162.4
ZNF507	ENST00000544431.5	c.11G>A	p.Ser4Asn	missense_variant	3/8	1		ENSP00000441549.1
ZNF507	ENST00000311921.8	c.11G>A	p.Ser4Asn	missense_variant	2/6	1		ENSP00000312277.2
ZNF507	ENST00000587084.5	n.266G>A		non_coding_transcript_exon_variant	3/4	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 24, 2024

The c.11G>A (p.S4N) alteration is located in exon 3 (coding exon 1) of the ZNF507 gene. This alteration results from a G to A substitution at nucleotide position 11, causing the serine (S) at amino acid position 4 to be replaced by an asparagine (N). 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	0.095
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.024	T;.;T
Eigen	Benign	0.0045
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.67	.;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.26	N;N;N
REVEL	Benign	0.074
Sift	Benign	0.046	D;D;D
Sift4G	Benign	0.18	T;T;T
Polyphen		0.18	B;.;B
Vest4		0.13
MutPred		0.16		Loss of phosphorylation at S4 (P = 0.0149);Loss of phosphorylation at S4 (P = 0.0149);Loss of phosphorylation at S4 (P = 0.0149);
MVP		0.39
MPC		0.054
ClinPred		0.32	T
GERP RS		3.2
Varity_R		0.17
gMVP		0.26

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.

Other links and lift over

hg19: chr19-32843747;