15-82990056-GGT-TCC

Variant names:

• chr15-82990056-GGT-TCC
• NM_031452.4:c.346_348delGGTinsTCC
• RAMAC p.Gly116Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_031452.4(RAMAC):​c.346_348delGGTinsTCC​(p.Gly116Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 25)
• Consequence: RAMAC NM_031452.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031452.4. 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
	RAMAC	NM_031452.4	MANE Select	c.346_348delGGTinsTCC	p.Gly116Ser	missense	N/A	NP_113640.1	Q9BTL3
	C15orf40	NM_001160116.2		c.367-901_367-899delACCinsGGA		intron	N/A	NP_001153588.1	Q8WUR7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAMAC	ENST00000304191.4	TSL:1 MANE Select	c.346_348delGGTinsTCC	p.Gly116Ser	missense	N/A	ENSP00000307181.3	Q9BTL3
	RAMAC	ENST00000933984.1		c.370_372delGGTinsTCC	p.Gly124Ser	missense	N/A	ENSP00000604043.1
	RAMAC	ENST00000875578.1		c.346_348delGGTinsTCC	p.Gly116Ser	missense	N/A	ENSP00000545637.1

Frequencies

GnomAD3 genomes Cov.: 25

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-83658808;