15-75207427-C-A

Variant names:

• chr15-75207427-C-A
• rs553765076
• NM_015492.5:c.1379C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015492.5(C15orf39):​c.1379C>A​(p.Pro460Gln) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P460L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C15orf39 NM_015492.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049660683).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015492.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C15orf39	NM_015492.5	MANE Select	c.1379C>A	p.Pro460Gln	missense	Exon 2 of 3	NP_056307.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C15orf39	ENST00000394987.5	TSL:1 MANE Select	c.1379C>A	p.Pro460Gln	missense	Exon 2 of 3	ENSP00000378438.4	Q6ZRI6-1
	C15orf39	ENST00000567617.1	TSL:1	c.1379C>A	p.Pro460Gln	missense	Exon 1 of 2	ENSP00000458025.1	Q6ZRI6-2
	C15orf39	ENST00000360639.6	TSL:2	c.1379C>A	p.Pro460Gln	missense	Exon 2 of 3	ENSP00000353854.2	Q6ZRI6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 92

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	10
DANN	Benign	0.85
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.60
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.034
Sift	Benign	0.051	T
Sift4G	Uncertain	0.018	D
Polyphen		0.47	P
Vest4		0.16
MutPred		0.18		Loss of catalytic residue at P460 (P = 0.0189)
MVP		0.14
MPC		0.20
ClinPred		0.13	T
GERP RS		1.6
Varity_R		0.032
gMVP		0.23

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: rs553765076; hg19: chr15-75499768;