Variant rs2290862 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018346.3(RSAD1):c.355G>A(p.Ala119Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 1,613,890 control chromosomes in the GnomAD database, including 302,979 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.66 ( 35303 hom., cov: 33)

Exomes 𝑓: 0.60 ( 267676 hom. )

Consequence

RSAD1
NM_018346.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.304

Variant links:

Genes affected

RSAD1 (HGNC:25634): (radical S-adenosyl methionine domain containing 1) Enables heme binding activity. Predicted to be involved in porphyrin-containing compound biosynthetic process. Predicted to be located in mitochondrion. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RSAD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.753465E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSAD1	NM_018346.3 linkuse as main transcript	c.355G>A	p.Ala119Thr	missense_variant	3/9	ENST00000258955.7	NP_060816.1
RSAD1	NR_130911.2 linkuse as main transcript	n.160+946G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSAD1	ENST00000258955.7 linkuse as main transcript	c.355G>A	p.Ala119Thr	missense_variant	3/9	1	NM_018346.3	ENSP00000258955	P1	Q9HA92-1

Frequencies

GnomAD3 genomes

AF:

0.663

AC:

100844

AN:

152006

Hom.:

35227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.867

Gnomad AMI

AF:

0.645

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.747

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.526

Gnomad FIN

AF:

0.533

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.603

Gnomad OTH

AF:

0.677

GnomAD3 exomes

AF:

0.588

AC:

147726

AN:

251122

Hom.:

46041

AF XY:

0.588

AC XY:

79789

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.880

Gnomad AMR exome

AF:

0.598

Gnomad ASJ exome

AF:

0.760

Gnomad EAS exome

AF:

0.204

Gnomad SAS exome

AF:

0.552

Gnomad FIN exome

AF:

0.534

Gnomad NFE exome

AF:

0.609

Gnomad OTH exome

AF:

0.621

GnomAD4 exome

AF:

0.599

AC:

875208

AN:

1461764

Hom.:

267676

Cov.:

AF XY:

0.598

AC XY:

434720

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.883

Gnomad4 AMR exome

AF:

0.601

Gnomad4 ASJ exome

AF:

0.750

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.556

Gnomad4 FIN exome

AF:

0.533

Gnomad4 NFE exome

AF:

0.604

Gnomad4 OTH exome

AF:

0.618

GnomAD4 genome

AF:

0.664

AC:

100988

AN:

152126

Hom.:

35303

Cov.:

AF XY:

0.656

AC XY:

48801

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.868

Gnomad4 AMR

AF:

0.638

Gnomad4 ASJ

AF:

0.747

Gnomad4 EAS

AF:

0.228

Gnomad4 SAS

AF:

0.527

Gnomad4 FIN

AF:

0.533

Gnomad4 NFE

AF:

0.603

Gnomad4 OTH

AF:

0.681

Alfa

AF:

0.621

Hom.:

40532

Bravo

AF:

0.683

TwinsUK

AF:

0.592

AC:

2196

ALSPAC

AF:

0.603

AC:

2324

ESP6500AA

AF:

0.868

AC:

3825

ESP6500EA

AF:

0.627

AC:

5389

ExAC

AF:

0.592

AC:

71849

Asia WGS

AF:

0.418

AC:

1456

AN:

3478

EpiCase

AF:

0.634

EpiControl

AF:

0.633

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.066

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.054

MetaRNN

Benign

7.8e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.050

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

0.74

REVEL

Benign

0.025

Sift

Benign

0.45

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.049

MPC

0.20

ClinPred

0.0015

GERP RS

0.020

Varity_R

0.022

gMVP

0.42

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over