Variant 15-82990021-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031452.4(RAMAC):c.311A>G(p.Tyr104Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000148 in 1,559,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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: 𝑓 0.000056 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RAMAC
NM_031452.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.77

Variant links:

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]

RAMAC links:

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

C15orf40 links:

ENSG00000259805 (HGNC:):

ENSG00000259805 links:

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ACMG classification

Classification made for transcript

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=0.06857085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAMAC	NM_031452.4 linkuse as main transcript	c.311A>G	p.Tyr104Cys	missense_variant	4/4	ENST00000304191.4	NP_113640.1	Q9BTL3
C15orf40	NM_001160116.2 linkuse as main transcript	c.367-864T>C		intron_variant			NP_001153588.1	Q8WUR7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAMAC	ENST00000304191.4 linkuse as main transcript	c.311A>G	p.Tyr104Cys	missense_variant	4/4	1	NM_031452.4	ENSP00000307181.3		Q9BTL3

Frequencies

GnomAD3 genomes

AF:

0.0000564

AC:

AN:

141750

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000337

AC:

AN:

237200

Hom.:

AF XY:

0.00000775

AC XY:

AN XY:

129000

show subpopulations

Gnomad AFR exome

AF:

0.000330

Gnomad AMR exome

AF:

0.0000961

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000106

AC:

AN:

1417320

Hom.:

Cov.:

AF XY:

0.00000854

AC XY:

AN XY:

702884

show subpopulations

Gnomad4 AFR exome

AF:

0.000342

Gnomad4 AMR exome

AF:

0.0000721

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:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000564

AC:

AN:

141750

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

68282

show subpopulations

Gnomad4 AFR

AF:

0.000213

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.311A>G (p.Y104C) alteration is located in exon 4 (coding exon 2) of the FAM103A1 gene. This alteration results from a A to G substitution at nucleotide position 311, causing the tyrosine (Y) at amino acid position 104 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

Benign

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.13

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.73

M_CAP

Benign

0.0027

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.10

Sift

Benign

0.045

Sift4G

Benign

0.14

Polyphen

0.0030

Vest4

0.42

MVP

0.14

MPC

0.58

ClinPred

0.069

GERP RS

3.0

Varity_R

0.10

gMVP

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over