Variant 10-69180304-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000359655.9(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. 12/21 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: 6.8e-7 ( 0 hom. )

Consequence

SUPV3L1
ENST00000359655.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.518

Variant links:

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]

SUPV3L1 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=0.18615401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUPV3L1	NM_003171.5 linkuse as main transcript	c.13C>G	p.Arg5Gly	missense_variant	1/15	ENST00000359655.9	NP_003162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SUPV3L1	ENST00000359655.9 linkuse as main transcript	c.13C>G	p.Arg5Gly	missense_variant	1/15	1	NM_003171.5	ENSP00000352678	P1
SUPV3L1	ENST00000471069.5 linkuse as main transcript	n.55C>G		non_coding_transcript_exon_variant	1/6	1
SUPV3L1	ENST00000422378.1 linkuse as main transcript	c.13C>G	p.Arg5Gly	missense_variant	1/6	5		ENSP00000409072
SUPV3L1	ENST00000483572.5 linkuse as main transcript	n.24C>G		non_coding_transcript_exon_variant	1/8	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461358

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726996

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:

8.99e-7

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

Feb 22, 2023

The c.13C>G (p.R5G) alteration is located in exon 1 (coding exon 1) of the SUPV3L1 gene. This alteration results from a C to G substitution at nucleotide position 13, causing the arginine (R) at amino acid position 5 to be replaced by a glycine (G). 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

0.14

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.38

T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.1

N;D

REVEL

Benign

0.093

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.049

B;.

Vest4

0.34

MutPred

0.39

Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);

MVP

0.31

MPC

1.2

ClinPred

0.96

GERP RS

3.9

Varity_R

0.41

gMVP

0.68

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