rs79736226

Variant names:

• chr8-124539151-C-G
• rs79736226
• NM_005005.3:c.-36C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-124539151-C-G
• chr8-124539151-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005005.3(NDUFB9):​c.-36C>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00116 in 1,613,684 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (6 hom.)
• Consequence: NDUFB9 NM_005005.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.91
• Publications: 1 publications found

Genes affected

NDUFB9 (HGNC:7704): (NADH:ubiquinone oxidoreductase subunit B9) The protein encoded by this gene is a subunit of the mitochondrial oxidative phosphorylation complex I (nicotinamide adenine dinucleotide: ubiquinone oxidoreductase). Complex I is localized to the inner mitochondrial membrane and functions to dehydrogenate nicotinamide adenine dinucleotide and to shuttle electrons to coenzyme Q. Complex I deficiency is the most common defect found in oxidative phosphorylation disorders and results in a range of conditions, including lethal neonatal disease, hypertrophic cardiomyopathy, liver disease, and adult-onset neurodegenerative disorders. Pseudogenes of this gene are found on chromosomes five, seven and eight. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

TATDN1 (HGNC:24220): (TatD DNase domain containing 1) Predicted to enable 3'-5'-exodeoxyribonuclease activity. Predicted to be involved in DNA metabolic process and nucleic acid phosphodiester bond hydrolysis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 8-124539151-C-G is Benign according to our data. Variant chr8-124539151-C-G is described in ClinVar as Benign. ClinVar VariationId is 138471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00575 (876/152388) while in subpopulation AFR AF = 0.0197 (820/41586). AF 95% confidence interval is 0.0186. There are 9 homozygotes in GnomAd4. There are 389 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005005.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB9	NM_005005.3	MANE Select	c.-36C>G		5_prime_UTR	Exon 1 of 4	NP_004996.1	Q9Y6M9
	NDUFB9	NM_001311168.2		c.-36C>G		5_prime_UTR	Exon 1 of 4	NP_001298097.1	E9PH64
	NDUFB9	NM_001278646.2		c.-163C>G		5_prime_UTR	Exon 1 of 4	NP_001265575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB9	ENST00000276689.8	TSL:1 MANE Select	c.-36C>G		5_prime_UTR	Exon 1 of 4	ENSP00000276689.3	Q9Y6M9
	NDUFB9	ENST00000518008.5	TSL:2	c.-36C>G		5_prime_UTR	Exon 1 of 3	ENSP00000428282.1	E7EWZ0
	NDUFB9	ENST00000928469.1		c.-36C>G		5_prime_UTR	Exon 1 of 4	ENSP00000598528.1

Frequencies

GnomAD3 genomes AF: 0.00575 AC: 876 AN: 152270 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00144 AC: 360 AN: 250552 AF XY: 0.00114

Gnomad AFR exome AF: 0.0191

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000679 AC: 992 AN: 1461296 Hom.: 6 Cov.: 32 AF XY: 0.000593 AC XY: 431 AN XY: 726964

African (AFR) AF: 0.0239 AC: 800 AN: 33470

American (AMR) AF: 0.00127 AC: 57 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111522

Other (OTH) AF: 0.00166 AC: 100 AN: 60374

GnomAD4 genome AF: 0.00575 AC: 876 AN: 152388 Hom.: 9 Cov.: 33 AF XY: 0.00522 AC XY: 389 AN XY: 74524

African (AFR) AF: 0.0197 AC: 820 AN: 41586

American (AMR) AF: 0.00261 AC: 40 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000827 AC: 4 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.000258 Hom.: 0

Bravo AF: 0.00637

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.74
PhyloP100		4.9
PromoterAI		0.41	Neutral
Mutation Taster		=296/4	polymorphism

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

Other links and lift over

dbSNP: rs79736226; hg19: chr8-125551392;