Variant 17-50482361-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018346.3(RSAD1):c.745G>C(p.Asp249His) variant causes a missense change. The variant allele was found at a frequency of 0.000768 in 1,611,512 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00080 ( 2 hom. )

Consequence

RSAD1
NM_018346.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14905149).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSAD1	NM_018346.3 linkuse as main transcript	c.745G>C	p.Asp249His	missense_variant	4/9	ENST00000258955.7	NP_060816.1
RSAD1	NR_130911.2 linkuse as main transcript	n.431G>C		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSAD1	ENST00000258955.7 linkuse as main transcript	c.745G>C	p.Asp249His	missense_variant	4/9	1	NM_018346.3	ENSP00000258955	P1	Q9HA92-1

Frequencies

GnomAD3 genomes

AF:

0.000466

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000515

AC:

128

AN:

248526

Hom.:

AF XY:

0.000514

AC XY:

AN XY:

134364

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0000876

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000946

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.000659

GnomAD4 exome

AF:

0.000800

AC:

1167

AN:

1459272

Hom.:

Cov.:

AF XY:

0.000780

AC XY:

566

AN XY:

725860

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000900

Gnomad4 ASJ exome

AF:

0.0000770

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000208

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.000564

GnomAD4 genome

AF:

0.000466

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000867

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000700

Hom.:

Bravo

AF:

0.000476

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000593

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.00107

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

Feb 13, 2024

The c.745G>C (p.D249H) alteration is located in exon 4 (coding exon 4) of the RSAD1 gene. This alteration results from a G to C substitution at nucleotide position 745, causing the aspartic acid (D) at amino acid position 249 to be replaced by a histidine (H). 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

0.22

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.77

M_CAP

Benign

0.035

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

0.94

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.17

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0070

Polyphen

0.74

Vest4

0.37

MVP

0.54

MPC

0.73

ClinPred

0.15

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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