19-32353215-C-T

Position:

• chr19-32353215-C-T

Variant summary

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

The NM_001136156.2(ZNF507):​c.385C>T​(p.Leu129Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 3.75

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 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	c.385C>T	p.Leu129Phe	missense_variant	3/7	ENST00000355898.6	NP_001129628.1
ZNF507	NM_014910.5	c.385C>T	p.Leu129Phe	missense_variant	2/6		NP_055725.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF507	ENST00000355898.6	c.385C>T	p.Leu129Phe	missense_variant	3/7	1	NM_001136156.2	ENSP00000348162.4
ZNF507	ENST00000544431.5	c.385C>T	p.Leu129Phe	missense_variant	3/8	1		ENSP00000441549.1
ZNF507	ENST00000311921.8	c.385C>T	p.Leu129Phe	missense_variant	2/6	1		ENSP00000312277.2
ZNF507	ENST00000587084.5	n.640C>T		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 01, 2024

The c.385C>T (p.L129F) alteration is located in exon 3 (coding exon 1) of the ZNF507 gene. This alteration results from a C to T substitution at nucleotide position 385, causing the leucine (L) at amino acid position 129 to be replaced by a phenylalanine (F). 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	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.3	M;.;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.62
MutPred		0.34		Gain of catalytic residue at L129 (P = 0.0705);Gain of catalytic residue at L129 (P = 0.0705);Gain of catalytic residue at L129 (P = 0.0705);
MVP		0.49
MPC		0.37
ClinPred		0.85	D
GERP RS		6.1
Varity_R		0.24
gMVP		0.17

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: chr19-32844121;