Variant 15-82990056-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.346G>A(p.Gly116Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0004 in 1,406,700 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 0.00020 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

RAMAC
NM_031452.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.78

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:

(HGNC:):

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:

Genome browser will be placed here

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=0.1970855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAMAC	NM_031452.4 linkuse as main transcript	c.346G>A	p.Gly116Ser	missense_variant	4/4	ENST00000304191.4	NP_113640.1
C15orf40	NM_001160116.2 linkuse as main transcript	c.367-899C>T		intron_variant			NP_001153588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAMAC	ENST00000304191.4 linkuse as main transcript	c.346G>A	p.Gly116Ser	missense_variant	4/4	1	NM_031452.4	ENSP00000307181	P1
	ENST00000566841.1 linkuse as main transcript	n.734+63439G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000202

AC:

AN:

133408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000576

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000160

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:

0.000363

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000165

AC:

AN:

188230

Hom.:

AF XY:

0.000204

AC XY:

AN XY:

102842

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000165

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000469

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000295

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.000421

AC:

536

AN:

1273292

Hom.:

Cov.:

AF XY:

0.000426

AC XY:

268

AN XY:

629542

show subpopulations

Gnomad4 AFR exome

AF:

0.0000351

Gnomad4 AMR exome

AF:

0.0000989

Gnomad4 ASJ exome

AF:

0.000141

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000293

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000504

Gnomad4 OTH exome

AF:

0.000605

GnomAD4 genome

AF:

0.000202

AC:

AN:

133408

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

63582

show subpopulations

Gnomad4 AFR

AF:

0.0000576

Gnomad4 AMR

AF:

0.000160

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000363

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000289

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000483

AC:

ExAC

AF:

0.000125

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

Oct 04, 2022

The c.346G>A (p.G116S) 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 346, causing the glycine (G) at amino acid position 116 to be replaced by a serine (S). 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

0.076

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.71

M_CAP

Benign

0.0063

MetaRNN

Benign

0.20

MetaSVM

Uncertain

-0.23

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.14

Sift

Benign

0.10

Sift4G

Benign

0.079

Polyphen

1.0

Vest4

0.11

MVP

0.20

MPC

0.66

ClinPred

0.19

GERP RS

5.6

Varity_R

0.15

gMVP

0.25

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