chr15-75207850-C-A

Variant names:

• chr15-75207850-C-A
• rs745391071
• NM_015492.5:c.1802C>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.1802C>A​(p.Ala601Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,142 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (1 hom.)
• Consequence: C15orf39 NM_015492.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.42
• 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=0.05732292).

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.1802C>A	p.Ala601Glu	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.1802C>A	p.Ala601Glu	missense	Exon 2 of 3	ENSP00000378438.4	Q6ZRI6-1
	C15orf39	ENST00000567617.1	TSL:1	c.1802C>A	p.Ala601Glu	missense	Exon 1 of 2	ENSP00000458025.1	Q6ZRI6-2
	C15orf39	ENST00000360639.6	TSL:2	c.1802C>A	p.Ala601Glu	missense	Exon 2 of 3	ENSP00000353854.2	Q6ZRI6-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461142 Hom.: 1 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726848

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52894

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111898

Other (OTH) AF: 0.0000497 AC: 3 AN: 60384

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.066
DANN	Benign	0.57
DEOGEN2	Benign	0.00077	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.81	L
PhyloP100		-1.4
PROVEAN	Benign	-0.83	N
REVEL	Uncertain	0.30
Sift	Benign	0.28	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.091
MutPred		0.10		Gain of methylation at K598 (P = 0.0828)
MVP		0.35
MPC		0.26
ClinPred		0.096	T
GERP RS		-6.2
Varity_R		0.077
gMVP		0.084
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: rs745391071; hg19: chr15-75500191;