10-69180304-C-G

Variant names:

• chr10-69180304-C-G
• rs1842010747
• NM_003171.5:c.13C>G

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.13C>G​(p.Arg5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,358 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. R5H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SUPV3L1 NM_003171.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.518
• Publications: 0 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=0.18615401).

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.13C>G	p.Arg5Gly	missense	Exon 1 of 15	NP_003162.2
	SUPV3L1	NM_001323585.2		c.-559C>G		5_prime_UTR	Exon 1 of 17	NP_001310514.1
	SUPV3L1	NM_001323586.2		c.-424C>G		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.13C>G	p.Arg5Gly	missense	Exon 1 of 15	ENSP00000352678.4	Q8IYB8
	SUPV3L1	ENST00000471069.5	TSL:1	n.55C>G		non_coding_transcript_exon	Exon 1 of 6
	SUPV3L1	ENST00000956079.1		c.13C>G	p.Arg5Gly	missense	Exon 1 of 16	ENSP00000626138.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461358 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726996

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53124

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60380

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

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	0.14
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.52
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.093
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.049	B
Vest4		0.34
MutPred		0.39		Loss of helix (P = 0.0068)
MVP		0.31
MPC		1.2
ClinPred		0.96	D
GERP RS		3.9
PromoterAI		0.19	Neutral
Varity_R		0.41
gMVP		0.68
Mutation Taster		=94/6	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: rs1842010747; hg19: chr10-70940060;