dbSNP rs753624288: NDUFA7:p.Ile8Phe (chr19-8321337-T-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005001.5(NDUFA7):c.22A>T(p.Ile8Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000038 in 1,579,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

NDUFA7
NM_005001.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

NDUFA7 (HGNC:7691): (NADH:ubiquinone oxidoreductase subunit A7) This gene encodes a subunit of NADH:ubiquinone oxidoreductase (complex I), which is a multiprotein complex located in the inner mitochondrial membrane. Complex I functions in the transfer of electrons from NADH to the respiratory chain. [provided by RefSeq, Mar 2011]

NDUFA7 links:

ENSG00000167774 (HGNC:):

ENSG00000167774 links:

RPS28 (HGNC:10418): (ribosomal protein S28) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S28E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.92

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA7	NM_005001.5 link	c.22A>T	p.Ile8Phe	missense_variant	Exon 1 of 4	ENST00000301457.3	NP_004992.2	O95182
NDUFA7	NR_135539.2 link	n.39A>T		non_coding_transcript_exon_variant	Exon 1 of 5
RPS28	NM_001031.5 link	c.-194T>A		upstream_gene_variant		ENST00000600659.3	NP_001022.1	P62857B2R4R9
RPS28	XM_047439201.1 link	c.-194T>A		upstream_gene_variant			XP_047295157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NDUFA7	ENST00000301457.3 link	c.22A>T	p.Ile8Phe	missense_variant	Exon 1 of 4	1	NM_005001.5	ENSP00000301457.1	O95182
ENSG00000167774	ENST00000598884.1 link	n.22A>T		non_coding_transcript_exon_variant	Exon 1 of 5	4		ENSP00000470609.1
RPS28	ENST00000600659.3 link	c.-194T>A		upstream_gene_variant		1	NM_001031.5	ENSP00000472469.1	P62857

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00000350

AC:

AN:

1427784

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707406

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:

0.00000364

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.0093

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.15

Eigen

Benign

0.054

Eigen_PC

Benign

-0.041

FATHMM_MKL

Uncertain

0.79

M_CAP

Benign

0.054

MetaRNN

Pathogenic

0.92

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.28

Sift

Benign

0.042

Sift4G

Uncertain

0.048

Polyphen

0.94

Vest4

0.81

MutPred

0.71

Gain of phosphorylation at S3 (P = 0.1875);

MVP

0.65

MPC

0.53

ClinPred

0.99

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.55

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over