rs756614086

Variant names:

• chr19-51994120-C-A
• rs756614086
• NM_001199324.2:c.989G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-51994120-C-A
• chr19-51994120-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199324.2(ZNF615):​c.989G>T​(p.Ser330Ile) 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. 13/22 in silico tools predict 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. S330N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF615 NM_001199324.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.10
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09795833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF615	NM_001199324.2	c.989G>T	p.Ser330Ile	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.989G>T	p.Ser330Ile	missense_variant	Exon 7 of 7	1	NM_001199324.2	ENSP00000471041.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251368 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0088	T;.;T;.;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.000050	N
LIST_S2	Benign	0.50	.;.;T;T;.;T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.098	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.;M;.;.;.;.
PhyloP100		-5.1
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-4.0	.;.;D;D;.;.;.
REVEL	Benign	0.034
Sift	Benign	0.061	.;.;T;T;.;.;.
Sift4G	Uncertain	0.052	T;D;T;T;D;D;D
Polyphen		0.60	P;P;P;.;P;.;P
Vest4		0.16
MutPred		0.38		Loss of disorder (P = 0.0112);.;Loss of disorder (P = 0.0112);.;.;.;.;
MVP		0.24
MPC		0.18
ClinPred		0.49	T
GERP RS		-2.8
Varity_R		0.16
gMVP		0.028
Mutation Taster		=99/1	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: rs756614086; hg19: chr19-52497373; COSMIC: COSV65034188; COSMIC: COSV65034188;