rs2290862

chr17-50479965-G-Achr17-50479965-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

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]

ACMG classification

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	UniProt
RSAD1	NM_018346.3	c.355G>A	p.Ala119Thr	missense_variant	3/9	ENST00000258955.7
RSAD1	NR_130911.2	n.160+946G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSAD1	ENST00000258955.7	c.355G>A	p.Ala119Thr	missense_variant	3/9	1	NM_018346.3	P1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100844 AN: 152006 Hom.: 35227 Cov.: 33

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

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.: 62 AF XY: 0.598 AC XY: 434720 AN XY: 727186

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.: 33 AF XY: 0.656 AC XY: 48801 AN XY: 74364

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	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	10
Dann	Benign	0.84
DEOGEN2	Benign	0.066	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.054	T
MetaRNN	Benign	7.8e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.050	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.74	N
REVEL	Benign	0.025
Sift	Benign	0.45	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.049
MPC		0.20
ClinPred		0.0015	T
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

Other links and lift over

dbSNP: rs2290862; hg19: chr17-48557326; COSMIC: COSV51955760; COSMIC: COSV51955760;