15-41387308-CA-C

Variant names:

• chr15-41387308-CA-C
• rs751327964
• ENST00000560978:c.*135delT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000560978(NDUFAF1):​c.*135delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (1 hom., cov: 30)
  • Exomes 𝑓: 0.23 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NDUFAF1 ENST00000560978 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.231

Genes affected

NDUFAF1 (HGNC:18828): (NADH:ubiquinone oxidoreductase complex assembly factor 1) This gene encodes a complex I assembly factor protein. Complex I (NADH-ubiquinone oxidoreductase) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. The encoded protein is required for assembly of complex I, and mutations in this gene are a cause of mitochondrial complex I deficiency. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 19. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-41387308-CA-C is Benign according to our data. Variant chr15-41387308-CA-C is described in ClinVar as [Benign]. Clinvar id is 1179686.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF1	NM_016013.4	c.*135delT		downstream_gene_variant		ENST00000260361.9	NP_057097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF1	ENST00000260361.9	c.*135delT		downstream_gene_variant		1	NM_016013.4	ENSP00000260361.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 409 AN: 66710 Hom.: 1 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.00253

Gnomad AMR AF: 0.00551

Gnomad ASJ AF: 0.00166

Gnomad EAS AF: 0.00134

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.0213

Gnomad NFE AF: 0.00279

Gnomad OTH AF: 0.00111

GnomAD3 exomes AF: 0.295 AC: 12260 AN: 41530 Hom.: 0 AF XY: 0.288 AC XY: 6236 AN XY: 21656

Gnomad AFR exome AF: 0.303

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.275

Gnomad EAS exome AF: 0.326

Gnomad SAS exome AF: 0.271

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.290

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.227 AC: 109621 AN: 483418 Hom.: 0 Cov.: 0 AF XY: 0.228 AC XY: 58078 AN XY: 255084

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00616 AC: 411 AN: 66728 Hom.: 1 Cov.: 30 AF XY: 0.00624 AC XY: 194 AN XY: 31112

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.00568

Gnomad4 ASJ AF: 0.00166

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.00500

Gnomad4 FIN AF: 0.0195

Gnomad4 NFE AF: 0.00280

Gnomad4 OTH AF: 0.00328

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs751327964; hg19: chr15-41679506;