21-42896966-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021075.4(NDUFV3):ā€‹c.88T>Cā€‹(p.Ser30Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

NDUFV3
NM_021075.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.109
Variant links:
Genes affected
NDUFV3 (HGNC:7719): (NADH:ubiquinone oxidoreductase subunit V3) The protein encoded by this gene is one of at least forty-one subunits that make up the NADH-ubiquinone oxidoreductase complex. This complex is part of the mitochondrial respiratory chain and serves to catalyze the rotenone-sensitive oxidation of NADH and the reduction of ubiquinone. The encoded protein is one of three proteins found in the flavoprotein fraction of the complex. The specific function of the encoded protein is unknown. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.042939246).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NDUFV3NM_021075.4 linkuse as main transcriptc.88T>C p.Ser30Pro missense_variant 2/4 ENST00000354250.7 NP_066553.3
NDUFV3NM_001001503.2 linkuse as main transcriptc.88T>C p.Ser30Pro missense_variant 2/3 NP_001001503.1
NDUFV3XM_011529586.3 linkuse as main transcriptc.88T>C p.Ser30Pro missense_variant 2/5 XP_011527888.1
NDUFV3XM_017028359.2 linkuse as main transcriptc.88T>C p.Ser30Pro missense_variant 2/4 XP_016883848.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NDUFV3ENST00000354250.7 linkuse as main transcriptc.88T>C p.Ser30Pro missense_variant 2/41 NM_021075.4 ENSP00000346196 P56181-2
NDUFV3ENST00000340344.4 linkuse as main transcriptc.88T>C p.Ser30Pro missense_variant 2/31 ENSP00000342895 P1P56181-1
NDUFV3ENST00000460259.1 linkuse as main transcriptn.611T>C non_coding_transcript_exon_variant 4/62
NDUFV3ENST00000460740.1 linkuse as main transcriptn.61+3585T>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152164
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461788
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152164
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

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 submitterclinical testingAmbry GeneticsFeb 02, 2024The c.88T>C (p.S30P) alteration is located in exon 2 (coding exon 2) of the NDUFV3 gene. This alteration results from a T to C substitution at nucleotide position 88, causing the serine (S) at amino acid position 30 to be replaced by a proline (P). 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
0.069
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
13
DANN
Benign
0.97
DEOGEN2
Benign
0.0025
.;T
Eigen
Benign
-0.96
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.035
N
LIST_S2
Benign
0.63
T;T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.043
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.94
L;L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.036
Sift
Benign
0.21
T;T
Sift4G
Benign
0.39
T;T
Polyphen
0.041
B;B
Vest4
0.25
MutPred
0.13
Loss of MoRF binding (P = 0.0451);Loss of MoRF binding (P = 0.0451);
MVP
0.16
MPC
0.14
ClinPred
0.14
T
GERP RS
-1.9
Varity_R
0.091
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs2058694511; hg19: chr21-44317076; API