rs767768198

Variant names:

• chr19-51993565-C-A
• rs767768198
• NM_001199324.2:c.1544G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-51993565-C-A
• chr19-51993565-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001199324.2(ZNF615):​c.1544G>T​(p.Arg515Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R515Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF615 NM_001199324.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 2 publications found

Genes affected

ZNF615 (HGNC:24740): (zinc finger protein 615) Predicted to enable DNA-binding transcription activator 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2707765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF615	NM_001199324.2	c.1544G>T	p.Arg515Leu	missense_variant	Exon 7 of 7	ENST00000598071.6	NP_001186253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF615	ENST00000598071.6	c.1544G>T	p.Arg515Leu	missense_variant	Exon 7 of 7	1	NM_001199324.2	ENSP00000471041.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T;.;T;.;.;.;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.00054	N
LIST_S2	Benign	0.52	.;.;T;T;.;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.27	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;M;.;.;.;.
PhyloP100		-0.25
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.4	.;.;D;D;.;.;.
REVEL	Benign	0.11
Sift	Uncertain	0.0020	.;.;D;D;.;.;.
Sift4G	Uncertain	0.0050	D;D;D;D;D;D;D
Polyphen		0.94	P;P;P;.;P;.;P
Vest4		0.28
MutPred		0.68		Loss of phosphorylation at T507 (P = 0.0625);.;Loss of phosphorylation at T507 (P = 0.0625);.;.;.;.;
MVP		0.43
MPC		0.28
ClinPred		0.95	D
GERP RS		2.9
Varity_R		0.45
gMVP		0.12
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs767768198; hg19: chr19-52496818;