chr8-124539210-C-T

Variant names:

• chr8-124539210-C-T
• rs147044660
• NM_005005.3:c.24C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005005.3(NDUFB9):​c.24C>T​(p.Pro8Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 1,614,228 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (5 hom.)
• Consequence: NDUFB9 NM_005005.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.549
• Publications: 2 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 8-124539210-C-T is Benign according to our data. Variant chr8-124539210-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.549 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 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.24C>T	p.Pro8Pro	synonymous	Exon 1 of 4	NP_004996.1	Q9Y6M9
	NDUFB9	NM_001311168.2		c.24C>T	p.Pro8Pro	synonymous	Exon 1 of 4	NP_001298097.1	E9PH64
	NDUFB9	NM_001278646.2		c.-104C>T		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.24C>T	p.Pro8Pro	synonymous	Exon 1 of 4	ENSP00000276689.3	Q9Y6M9
	NDUFB9	ENST00000901305.1		c.24C>T	p.Pro8Pro	synonymous	Exon 1 of 5	ENSP00000571364.1
	NDUFB9	ENST00000518008.5	TSL:2	c.24C>T	p.Pro8Pro	synonymous	Exon 1 of 3	ENSP00000428282.1	E7EWZ0

Frequencies

GnomAD3 genomes AF: 0.00248 AC: 377 AN: 152244 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00241

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00199 AC: 500 AN: 251332 AF XY: 0.00197

Gnomad AFR exome AF: 0.00296

Gnomad AMR exome AF: 0.00309

Gnomad ASJ exome AF: 0.00327

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000831

Gnomad NFE exome AF: 0.00242

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00255 AC: 3722 AN: 1461868 Hom.: 5 Cov.: 32 AF XY: 0.00246 AC XY: 1790 AN XY: 727236

African (AFR) AF: 0.00323 AC: 108 AN: 33480

American (AMR) AF: 0.00300 AC: 134 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00283 AC: 74 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.000374 AC: 20 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00289 AC: 3215 AN: 1111998

Other (OTH) AF: 0.00283 AC: 171 AN: 60396

GnomAD4 genome AF: 0.00247 AC: 377 AN: 152360 Hom.: 3 Cov.: 33 AF XY: 0.00216 AC XY: 161 AN XY: 74510

African (AFR) AF: 0.00250 AC: 104 AN: 41588

American (AMR) AF: 0.00568 AC: 87 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00241 AC: 164 AN: 68034

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00215 Hom.: 0

Bravo AF: 0.00301

EpiCase AF: 0.00256

EpiControl AF: 0.00273

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Mitochondrial complex I deficiency, nuclear type 24 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.1
DANN	Benign	0.86
PhyloP100		-0.55
PromoterAI		0.014	Neutral
Mutation Taster		=99/1	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: rs147044660; hg19: chr8-125551451;