17-50479965-G-C

Variant names:

• chr17-50479965-G-C
• rs2290862
• NM_018346.3:c.355G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018346.3(RSAD1):​c.355G>C​(p.Ala119Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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: not found (cov: 33)
• Consequence: RSAD1 NM_018346.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10304764).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018346.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSAD1	NM_018346.3	MANE Select	c.355G>C	p.Ala119Pro	missense	Exon 3 of 9	NP_060816.1	Q9HA92-1
	RSAD1	NR_130911.2		n.160+946G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSAD1	ENST00000258955.7	TSL:1 MANE Select	c.355G>C	p.Ala119Pro	missense	Exon 3 of 9	ENSP00000258955.2	Q9HA92-1
	RSAD1	ENST00000859049.1		c.388G>C	p.Ala130Pro	missense	Exon 3 of 9	ENSP00000529108.1
	RSAD1	ENST00000859052.1		c.355G>C	p.Ala119Pro	missense	Exon 3 of 9	ENSP00000529111.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
PhyloP100		0.30
Varity_R		0.43
gMVP		0.79

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2290862; hg19: chr17-48557326;