rs755924435

Variant names:

• chr15-82989090-G-A
• NM_031452.4:c.72G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-82989090-G-A
• chr15-82989090-G-T

Variant summary

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

The NM_001160116.2(C15orf40):​c.434C>T​(p.Pro145Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C15orf40 NM_001160116.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

Genes affected

RAMAC (HGNC:31022): (RNA guanine-7 methyltransferase activating subunit) Enables RNA binding activity and enzyme activator activity. Involved in methylation and recruitment of mRNA capping enzyme to RNA polymerase II holoenzyme complex. Located in nucleoplasm. Part of mRNA cap binding activity complex and mRNA cap methyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

C15orf40 (HGNC:28443): (chromosome 15 open reading frame 40) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259805 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031551808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAMAC	NM_031452.4	c.72G>A	p.Lys24Lys	synonymous_variant	Exon 3 of 4	ENST00000304191.4	NP_113640.1
C15orf40	NM_001160116.2	c.434C>T	p.Pro145Leu	missense_variant	Exon 4 of 4		NP_001153588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAMAC	ENST00000304191.4	c.72G>A	p.Lys24Lys	synonymous_variant	Exon 3 of 4	1	NM_031452.4	ENSP00000307181.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461504 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727070

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.4
DANN	Benign	0.97
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	0.91	N
REVEL	Benign	0.050
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.14
MutPred		0.47		Loss of disorder (P = 0.0085);
MVP		0.24
ClinPred		0.067	T
GERP RS		3.4

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-83657842;