dbSNP rs557506481: NDUFAF5:c.-26G>T (chr20-13785043-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_024120.5(NDUFAF5):c.-26G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000476 in 1,597,638 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

NDUFAF5
NM_024120.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.419

Publications

0 publications found

Variant links:

Genes affected

NDUFAF5 (HGNC:15899): (NADH:ubiquinone oxidoreductase complex assembly factor 5) The NADH-ubiquinone oxidoreductase complex (complex I) of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. This gene encodes a mitochondrial protein that is associated with the matrix face of the mitochondrial inner membrane and is required for complex I assembly. A mutation in this gene results in mitochondrial complex I deficiency. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

NDUFAF5 links:

ESF1 (HGNC:15898): (ESF1 nucleolar pre-rRNA processing protein homolog) Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ESF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 20-13785043-G-T is Benign according to our data. Variant chr20-13785043-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 510083.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024120.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NDUFAF5	NM_024120.5	MANE Select	c.-26G>T	5_prime_UTR	Exon 1 of 11	NP_077025.2
NDUFAF5	NM_001039375.3		c.-26G>T	5_prime_UTR	Exon 1 of 10	NP_001034464.1	Q5TEU4-2
NDUFAF5	NM_001352408.2		c.-26G>T	5_prime_UTR	Exon 1 of 9	NP_001339337.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NDUFAF5	ENST00000378106.10	TSL:1 MANE Select	c.-26G>T	5_prime_UTR	Exon 1 of 11	ENSP00000367346.5	Q5TEU4-1
NDUFAF5	ENST00000874783.1		c.-26G>T	5_prime_UTR	Exon 1 of 12	ENSP00000544842.1
NDUFAF5	ENST00000949288.1		c.-26G>T	5_prime_UTR	Exon 1 of 10	ENSP00000619347.1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000920

AC:

AN:

228278

AF XY:

0.000120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000443

AC:

AN:

1445276

Hom.:

Cov.:

AF XY:

0.0000709

AC XY:

AN XY:

718872

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33152

American (AMR)

AF:

0.00

AC:

AN:

43674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25896

East Asian (EAS)

AF:

0.00

AC:

AN:

39398

South Asian (SAS)

AF:

0.000671

AC:

AN:

84928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4356

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1105040

Other (OTH)

AF:

0.0000838

AC:

AN:

59700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41594

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00248

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.73

PhyloP100

-0.42

PromoterAI

0.097

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over