8-124539326-C-T

Variant names:

• chr8-124539326-C-T
• rs7010411
• NM_005005.3:c.101+39C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005005.3(NDUFB9):​c.101+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,605,236 control chromosomes in the GnomAD database, including 63,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5729 hom., cov: 32)
  • Exomes 𝑓: 0.28 (58014 hom.)
• Consequence: NDUFB9 NM_005005.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.851
• Publications: 12 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=-0.83).
• BP6: Variant 8-124539326-C-T is Benign according to our data. Variant chr8-124539326-C-T is described in ClinVar as Benign. ClinVar VariationId is 1291363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

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.101+39C>T		intron	N/A	NP_004996.1	Q9Y6M9
	NDUFB9	NM_001311168.2		c.101+39C>T		intron	N/A	NP_001298097.1	E9PH64
	NDUFB9	NM_001278646.2		c.-27+39C>T		intron	N/A	NP_001265575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB9	ENST00000276689.8	TSL:1 MANE Select	c.101+39C>T		intron	N/A	ENSP00000276689.3	Q9Y6M9
	TATDN1	ENST00000523152.3	TSL:5	c.-280G>A		5_prime_UTR	Exon 1 of 4	ENSP00000427807.1	E5RG62
	NDUFB9	ENST00000901305.1		c.101+39C>T		intron	N/A	ENSP00000571364.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40763 AN: 151928 Hom.: 5728 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.254

GnomAD2 exomes AF: 0.283 AC: 69929 AN: 246854 AF XY: 0.293

Gnomad AFR exome AF: 0.271

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.375

Gnomad FIN exome AF: 0.353

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.274

GnomAD4 exome AF: 0.276 AC: 401141 AN: 1453190 Hom.: 58014 Cov.: 29 AF XY: 0.281 AC XY: 203233 AN XY: 723434

African (AFR) AF: 0.271 AC: 9037 AN: 33334

American (AMR) AF: 0.139 AC: 6230 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 7108 AN: 26080

East Asian (EAS) AF: 0.411 AC: 16286 AN: 39626

South Asian (SAS) AF: 0.431 AC: 37050 AN: 86058

European-Finnish (FIN) AF: 0.354 AC: 18844 AN: 53216

Middle Eastern (MID) AF: 0.324 AC: 1861 AN: 5746

European-Non Finnish (NFE) AF: 0.260 AC: 287431 AN: 1104398

Other (OTH) AF: 0.288 AC: 17294 AN: 60048

GnomAD4 genome AF: 0.268 AC: 40763 AN: 152046 Hom.: 5729 Cov.: 32 AF XY: 0.276 AC XY: 20484 AN XY: 74302

African (AFR) AF: 0.266 AC: 11027 AN: 41488

American (AMR) AF: 0.178 AC: 2721 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1904 AN: 5150

South Asian (SAS) AF: 0.442 AC: 2128 AN: 4814

European-Finnish (FIN) AF: 0.357 AC: 3769 AN: 10572

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17506 AN: 67954

Other (OTH) AF: 0.252 AC: 533 AN: 2114

Alfa AF: 0.246 Hom.: 6190

Bravo AF: 0.251

Asia WGS AF: 0.387 AC: 1343 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.94
PhyloP100		-0.85
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs7010411; hg19: chr8-125551567; COSMIC: COSV52674207; COSMIC: COSV52674207;