Genetic Variant NM_018346.3:c.355G>A (chr17-50479965-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 0.66 ( 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

Publications

42 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RSAD1	NM_018346.3 link	c.355G>A	p.Ala119Thr	missense_variant	Exon 3 of 9	ENST00000258955.7	NP_060816.1	Q9HA92-1
RSAD1	NR_130911.2 link	n.160+946G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSAD1	ENST00000258955.7 link	c.355G>A	p.Ala119Thr	missense_variant	Exon 3 of 9	1	NM_018346.3	ENSP00000258955.2		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

GnomAD2 exomes

AF:

0.588

AC:

147726

AN:

251122

AF XY:

0.588

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 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

African (AFR)

AF:

0.883

AC:

29573

AN:

33480

American (AMR)

AF:

0.601

AC:

26892

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

19612

AN:

26136

East Asian (EAS)

AF:

0.232

AC:

9197

AN:

39700

South Asian (SAS)

AF:

0.556

AC:

47940

AN:

86256

European-Finnish (FIN)

AF:

0.533

AC:

28447

AN:

53344

Middle Eastern (MID)

AF:

0.732

AC:

4221

AN:

5768

European-Non Finnish (NFE)

AF:

0.604

AC:

671978

AN:

1111964

Other (OTH)

AF:

0.618

AC:

37348

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

21484

42968

64453

85937

107421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18130

36260

54390

72520

90650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.664

AC:

100988

AN:

152126

Hom.:

35303

Cov.:

AF XY:

0.656

AC XY:

48801

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.868

AC:

36030

AN:

41512

American (AMR)

AF:

0.638

AC:

9756

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.747

AC:

2591

AN:

3470

East Asian (EAS)

AF:

0.228

AC:

1178

AN:

5170

South Asian (SAS)

AF:

0.527

AC:

2543

AN:

4822

European-Finnish (FIN)

AF:

0.533

AC:

5634

AN:

10570

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.603

AC:

41009

AN:

67972

Other (OTH)

AF:

0.681

AC:

1439

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1603

3206

4810

6413

8016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

770

1540

2310

3080

3850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.621

Hom.:

61889

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

(source)

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

PhyloP100

0.30

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over