Variant 17-50478952-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_018346.3(RSAD1):c.68G>A(p.Arg23His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000806 in 1,240,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.1e-7 ( 0 hom. )

Consequence

RSAD1
NM_018346.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.955

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:

RSAD1 (HGNC:):

RSAD1 links:

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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=0.07129902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSAD1	NM_018346.3 linkuse as main transcript	c.68G>A	p.Arg23His	missense_variant	1/9	ENST00000258955.7	NP_060816.1	Q9HA92-1
RSAD1	NR_130911.2 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RSAD1	ENST00000258955.7 linkuse as main transcript	c.68G>A	p.Arg23His	missense_variant	1/9	1	NM_018346.3	ENSP00000258955.2	Q9HA92-1
RSAD1	ENST00000443328.2 linkuse as main transcript	n.93G>A		non_coding_transcript_exon_variant	1/3	2
RSAD1	ENST00000504284.1 linkuse as main transcript	n.50G>A		non_coding_transcript_exon_variant	1/8	5		ENSP00000425372.1	H0Y9X4
RSAD1	ENST00000515221.2 linkuse as main transcript	n.68G>A		non_coding_transcript_exon_variant	1/5	2		ENSP00000424558.2	Q9HA92-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.06e-7

AC:

AN:

1240196

Hom.:

Cov.:

AF XY:

0.00000164

AC XY:

AN XY:

607914

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 22, 2024

The c.68G>A (p.R23H) alteration is located in exon 1 (coding exon 1) of the RSAD1 gene. This alteration results from a G to A substitution at nucleotide position 68, causing the arginine (R) at amino acid position 23 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

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.5

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0066

LIST_S2

Benign

0.54

M_CAP

Benign

0.021

MetaRNN

Benign

0.071

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.57

REVEL

Benign

0.0090

Sift

Benign

0.060

Sift4G

Benign

0.20

Polyphen

0.0020

Vest4

0.084

MutPred

0.37

Loss of MoRF binding (P = 0.0308);

MVP

0.14

MPC

0.25

ClinPred

0.42

GERP RS

-7.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.089

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over