Variant 15-82989888-G-A 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.178G>A(p.Asp60Asn) variant causes a missense change involving the alteration of a conserved nucleotide. 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAMAC
NM_031452.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.40

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=0.24266511).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAMAC	NM_031452.4 linkuse as main transcript	c.178G>A	p.Asp60Asn	missense_variant	4/4	ENST00000304191.4	NP_113640.1	Q9BTL3
C15orf40	NM_001160116.2 linkuse as main transcript	c.367-731C>T		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.178G>A	p.Asp60Asn	missense_variant	4/4	1	NM_031452.4	ENSP00000307181.3		Q9BTL3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249322

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1460288

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726446

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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

Jul 30, 2023

The c.178G>A (p.D60N) alteration is located in exon 4 (coding exon 2) of the FAM103A1 gene. This alteration results from a G to A substitution at nucleotide position 178, causing the aspartic acid (D) at amino acid position 60 to be replaced by an asparagine (N). 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

0.27

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

M_CAP

Benign

0.0090

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.53

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.21

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.037

Polyphen

0.59

Vest4

0.44

MutPred

0.39

Gain of methylation at R57 (P = 0.0688);

MVP

0.19

MPC

0.85

ClinPred

0.96

GERP RS

5.5

Varity_R

0.32

gMVP

0.37

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