NM_003171.5:c.217G>C

Variant names:

• chr10-69180508-G-C
• rs201283581
• NM_003171.5:c.217G>C

Variant summary

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

The NM_003171.5(SUPV3L1):​c.217G>C​(p.Gly73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G73S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SUPV3L1 NM_003171.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69
• Publications: 2 publications found

Genes affected

SUPV3L1 (HGNC:11471): (Suv3 like RNA helicase) Enables helicase activity; nucleic acid binding activity; and protein homodimerization activity. Involved in several processes, including mitochondrial RNA metabolic process; mitochondrion morphogenesis; and positive regulation of mitochondrial RNA catabolic process. Located in mitochondrial nucleoid and nucleus. Part of mitochondrial degradosome. [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=0.1046541).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003171.5. 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
	SUPV3L1	NM_003171.5	MANE Select	c.217G>C	p.Gly73Arg	missense	Exon 1 of 15	NP_003162.2
	SUPV3L1	NM_001323585.2		c.-355G>C		5_prime_UTR	Exon 1 of 17	NP_001310514.1
	SUPV3L1	NM_001323586.2		c.-220G>C		5_prime_UTR	Exon 1 of 16	NP_001310515.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUPV3L1	ENST00000359655.9	TSL:1 MANE Select	c.217G>C	p.Gly73Arg	missense	Exon 1 of 15	ENSP00000352678.4	Q8IYB8
	SUPV3L1	ENST00000471069.5	TSL:1	n.259G>C		non_coding_transcript_exon	Exon 1 of 6
	SUPV3L1	ENST00000956079.1		c.217G>C	p.Gly73Arg	missense	Exon 1 of 16	ENSP00000626138.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152250 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1112010

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152250 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.061
Eigen_PC	Benign	0.099
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.7
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.067
Sift	Benign	0.40	T
Sift4G	Benign	0.55	T
Polyphen		0.45	P
Vest4		0.38
MutPred		0.13		Loss of catalytic residue at G73 (P = 0.0454)
MVP		0.44
MPC		0.41
ClinPred		0.25	T
GERP RS		4.8
PromoterAI		-0.079	Neutral
Varity_R		0.28
gMVP		0.44
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs201283581; hg19: chr10-70940264;