rs182425183

Variant names:

• chr15-75207166-C-G
• rs182425183
• NM_015492.5:c.1118C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-75207166-C-G
• chr15-75207166-C-T

Variant summary

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

The NM_015492.5(C15orf39):​c.1118C>G​(p.Pro373Arg) 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. 13/20 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. P373L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 29)
• Consequence: C15orf39 NM_015492.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27

Genes affected

C15orf39 (HGNC:24497): (chromosome 15 open reading frame 39) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.22842804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C15orf39	NM_015492.5	c.1118C>G	p.Pro373Arg	missense_variant	Exon 2 of 3	ENST00000394987.5	NP_056307.3
C15orf39	XM_047432864.1	c.1118C>G	p.Pro373Arg	missense_variant	Exon 3 of 4		XP_047288820.1
C15orf39	XM_047432865.1	c.284C>G	p.Pro95Arg	missense_variant	Exon 4 of 5		XP_047288821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C15orf39	ENST00000394987.5	c.1118C>G	p.Pro373Arg	missense_variant	Exon 2 of 3	1	NM_015492.5	ENSP00000378438.4
C15orf39	ENST00000567617.1	c.1118C>G	p.Pro373Arg	missense_variant	Exon 1 of 2	1		ENSP00000458025.1
C15orf39	ENST00000360639.6	c.1118C>G	p.Pro373Arg	missense_variant	Exon 2 of 3	2		ENSP00000353854.2
C15orf39	ENST00000565074.1	c.722C>G	p.Pro241Arg	missense_variant	Exon 1 of 1	6		ENSP00000454405.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.0064	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.056	T;T;.
Eigen	Benign	0.033
Eigen_PC	Benign	-0.065
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.73	.;T;T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.9	L;L;L
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.90	P;P;.
Vest4		0.36
MutPred		0.35		Gain of solvent accessibility (P = 0.0055);Gain of solvent accessibility (P = 0.0055);Gain of solvent accessibility (P = 0.0055);
MVP		0.15
MPC		0.77
ClinPred		0.97	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs182425183; hg19: chr15-75499507;