15-75206602-C-G

Variant names:

• chr15-75206602-C-G
• rs151171215
• NM_015492.5:c.554C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_015492.5(C15orf39):​c.554C>G​(p.Thr185Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000402 in 1,613,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (0 hom.)
• Consequence: C15orf39 NM_015492.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.616

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0025666654).
• BP6: Variant 15-75206602-C-G is Benign according to our data. Variant chr15-75206602-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2229647.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C15orf39	NM_015492.5	c.554C>G	p.Thr185Ser	missense_variant	Exon 2 of 3	ENST00000394987.5	NP_056307.3
C15orf39	XM_047432864.1	c.554C>G	p.Thr185Ser	missense_variant	Exon 3 of 4		XP_047288820.1
C15orf39	XM_047432865.1	c.88C>G	p.Leu30Val	missense_variant	Exon 3 of 5		XP_047288821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C15orf39	ENST00000394987.5	c.554C>G	p.Thr185Ser	missense_variant	Exon 2 of 3	1	NM_015492.5	ENSP00000378438.4
C15orf39	ENST00000567617.1	c.554C>G	p.Thr185Ser	missense_variant	Exon 1 of 2	1		ENSP00000458025.1
C15orf39	ENST00000360639.6	c.554C>G	p.Thr185Ser	missense_variant	Exon 2 of 3	2		ENSP00000353854.2
C15orf39	ENST00000565074.1	c.158C>G	p.Thr53Ser	missense_variant	Exon 1 of 1	6		ENSP00000454405.1

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 66 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000643 AC: 161 AN: 250484 Hom.: 0 AF XY: 0.000619 AC XY: 84 AN XY: 135652

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.0131

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000195

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000399 AC: 583 AN: 1461558 Hom.: 0 Cov.: 80 AF XY: 0.000417 AC XY: 303 AN XY: 727094

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.0143

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000117

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.000434 AC: 66 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74350

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.000956

Alfa AF: 0.00145 Hom.: 1

Bravo AF: 0.000461

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000815 AC: 7

ExAC AF: 0.000511 AC: 62

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 22, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.74
DEOGEN2	Benign	0.00028	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.35	.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.0026	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.4	N;N;N
PROVEAN	Benign	0.73	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.80	T;T;T
Sift4G	Benign	0.81	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.032
MutPred		0.089		Loss of phosphorylation at T185 (P = 0.0755);Loss of phosphorylation at T185 (P = 0.0755);Loss of phosphorylation at T185 (P = 0.0755);
MVP		0.11
MPC		0.19
ClinPred		0.0071	T
GERP RS		1.8
Varity_R		0.037
gMVP		0.084

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: rs151171215; hg19: chr15-75498943;