15-82989956-G-T

Position:

• chr15-82989956-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031452.4(RAMAC):​c.246G>T​(p.Trp82Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RAMAC NM_031452.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71

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]

(HGNC:):

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24922791).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAMAC	NM_031452.4	c.246G>T	p.Trp82Cys	missense_variant	4/4	ENST00000304191.4	NP_113640.1
C15orf40	NM_001160116.2	c.367-799C>A		intron_variant			NP_001153588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAMAC	ENST00000304191.4	c.246G>T	p.Trp82Cys	missense_variant	4/4	1	NM_031452.4	ENSP00000307181	P1
	ENST00000566841.1	n.734+63339G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 22, 2021

The c.246G>T (p.W82C) alteration is located in exon 4 (coding exon 2) of the FAM103A1 gene. This alteration results from a G to T substitution at nucleotide position 246, causing the tryptophan (W) at amino acid position 82 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.46	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.23
Sift	Benign	0.081	T
Sift4G	Uncertain	0.051	T
Polyphen		1.0	D
Vest4		0.45
MutPred		0.31		Loss of solvent accessibility (P = 0.0442);
MVP		0.068
MPC		0.88
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.30
gMVP		0.36

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: chr15-83658708;