15-75207850-C-T

Variant names:

• chr15-75207850-C-T
• rs745391071
• NM_015492.5:c.1802C>T

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>T​(p.Ala601Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,461,142 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A601E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: C15orf39 NM_015492.5 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.061796427).

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>T	p.Ala601Val	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>T	p.Ala601Val	missense	Exon 2 of 3	ENSP00000378438.4	Q6ZRI6-1
	C15orf39	ENST00000567617.1	TSL:1	c.1802C>T	p.Ala601Val	missense	Exon 1 of 2	ENSP00000458025.1	Q6ZRI6-2
	C15orf39	ENST00000360639.6	TSL:2	c.1802C>T	p.Ala601Val	missense	Exon 2 of 3	ENSP00000353854.2	Q6ZRI6-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250230 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

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 AF: 0.0000233 AC: 34 AN: 1461142 Hom.: 0 Cov.: 34 AF XY: 0.0000234 AC XY: 17 AN XY: 726848

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

American (AMR) AF: 0.0000224 AC: 1 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: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111898

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.31
DANN	Benign	0.64
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.81	L
PhyloP100		-1.4
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.22
Sift	Benign	0.065	T
Sift4G	Benign	0.18	T
Polyphen		0.0020	B
Vest4		0.026
MutPred		0.20		Gain of sheet (P = 0.0166)
MVP		0.43
MPC		0.22
ClinPred		0.056	T
GERP RS		-6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.082
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;