17-50482196-G-C

Position:

• chr17-50482196-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018346.3(RSAD1):​c.580G>C​(p.Val194Leu) 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. 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: 32)
• Consequence: RSAD1 NM_018346.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21

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 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=0.25789273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSAD1	NM_018346.3	c.580G>C	p.Val194Leu	missense_variant	4/9	ENST00000258955.7	NP_060816.1
RSAD1	NR_130911.2	n.266G>C		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSAD1	ENST00000258955.7	c.580G>C	p.Val194Leu	missense_variant	4/9	1	NM_018346.3	ENSP00000258955	P1
RSAD1	ENST00000506211.1	c.100G>C	p.Val34Leu	missense_variant, NMD_transcript_variant	1/6	3		ENSP00000422893
RSAD1	ENST00000515221.2	c.241G>C	p.Val81Leu	missense_variant, NMD_transcript_variant	2/5	2		ENSP00000424558
RSAD1	ENST00000504284.1	c.*99G>C		3_prime_UTR_variant, NMD_transcript_variant	3/8	5		ENSP00000425372

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

The c.580G>C (p.V194L) 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 580, causing the valine (V) at amino acid position 194 to be replaced by a leucine (L). 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	0.27
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.051
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.38	N
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.034
Sift	Benign	0.17	T
Sift4G	Benign	0.22	T
Polyphen		0.033	B
Vest4		0.20
MutPred		0.70		Gain of sheet (P = 0.0827);
MVP		0.095
MPC		0.22
ClinPred		0.78	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.62

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.

Other links and lift over

hg19: chr17-48559557;