rs372110976

Variant names:

• chr15-82989977-C-A
• rs372110976
• NM_031452.4:c.267C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-82989977-C-A
• chr15-82989977-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031452.4(RAMAC):​c.267C>A​(p.Asn89Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000636 in 1,604,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: RAMAC NM_031452.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0690
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018187374).

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.267C>A	p.Asn89Lys	missense	Exon 4 of 4	NP_113640.1	Q9BTL3
	C15orf40	NM_001160116.2		c.367-820G>T		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.267C>A	p.Asn89Lys	missense	Exon 4 of 4	ENSP00000307181.3	Q9BTL3
	RAMAC	ENST00000933984.1		c.291C>A	p.Asn97Lys	missense	Exon 4 of 4	ENSP00000604043.1
	RAMAC	ENST00000875578.1		c.267C>A	p.Asn89Lys	missense	Exon 5 of 5	ENSP00000545637.1

Frequencies

GnomAD3 genomes AF: 0.000441 AC: 66 AN: 149678 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000671

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000444

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000845 AC: 21 AN: 248538 AF XY: 0.0000595

Gnomad AFR exome AF: 0.00125

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000247 AC: 36 AN: 1454594 Hom.: 0 Cov.: 28 AF XY: 0.0000221 AC XY: 16 AN XY: 723906

African (AFR) AF: 0.00102 AC: 34 AN: 33336

American (AMR) AF: 0.00 AC: 0 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 86014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105758

Other (OTH) AF: 0.0000166 AC: 1 AN: 60148

GnomAD4 genome AF: 0.000441 AC: 66 AN: 149792 Hom.: 0 Cov.: 31 AF XY: 0.000397 AC XY: 29 AN XY: 72986

African (AFR) AF: 0.00153 AC: 62 AN: 40588

American (AMR) AF: 0.0000670 AC: 1 AN: 14920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.00 AC: 0 AN: 4628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000444 AC: 3 AN: 67586

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000412

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000107 AC: 13

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	Uncertain	0.53
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.68	T
PhyloP100		-0.069
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.057
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.067	T
Polyphen		0.21	B
Vest4		0.48
MutPred		0.29		Gain of methylation at N89 (P = 8e-04)
MVP		0.082
MPC		0.68
ClinPred		0.13	T
GERP RS		1.1
Varity_R		0.12
gMVP		0.28
Mutation Taster		=76/24	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: rs372110976; hg19: chr15-83658729;