Variant 10-69199143-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003171.5(SUPV3L1):c.1244A>G(p.Asn415Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,612,856 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

SUPV3L1
NM_003171.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

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:

SUPV3L1 (HGNC:):

SUPV3L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03159383).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUPV3L1	NM_003171.5 linkuse as main transcript	c.1244A>G	p.Asn415Ser	missense_variant	10/15	ENST00000359655.9	NP_003162.2	Q8IYB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUPV3L1	ENST00000359655.9 linkuse as main transcript	c.1244A>G	p.Asn415Ser	missense_variant	10/15	1	NM_003171.5	ENSP00000352678.4		Q8IYB8
SUPV3L1	ENST00000422378.1 linkuse as main transcript	c.662A>G	p.Asn221Ser	missense_variant	5/6	5		ENSP00000409072.1		B1AR60

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD3 exomes

AF:

0.0000561

AC:

AN:

249732

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

134954

show subpopulations

Gnomad AFR exome

AF:

0.000618

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1460490

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726496

show subpopulations

Gnomad4 AFR exome

AF:

0.000868

Gnomad4 AMR exome

AF:

0.0000450

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000269

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000193

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3474

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

Apr 04, 2023

The c.1244A>G (p.N415S) alteration is located in exon 10 (coding exon 10) of the SUPV3L1 gene. This alteration results from a A to G substitution at nucleotide position 1244, causing the asparagine (N) at amino acid position 415 to be replaced by a serine (S). 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

0.053

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.30

T;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.36

N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.031

Sift

Benign

0.30

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0

B;.

Vest4

0.17

MVP

0.37

MPC

0.24

ClinPred

0.011

GERP RS

0.50

Varity_R

0.054

gMVP

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over