19-14572039-C-A

Variant names:

• chr19-14572039-C-A
• rs45628939
• NM_004146.6:c.-39G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004146.6(NDUFB7):​c.-39G>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 0.00000226 in 1,325,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: NDUFB7 NM_004146.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63
• Publications: 0 publications found

Genes affected

NDUFB7 (HGNC:7702): (NADH:ubiquinone oxidoreductase subunit B7) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is composed of 45 different subunits. It is located at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. [provided by RefSeq, Jul 2008]

NDUFB7 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 39

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004146.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB7	NM_004146.6	MANE Select	c.-39G>T		5_prime_UTR	Exon 1 of 3	NP_004137.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFB7	ENST00000215565.3	TSL:1 MANE Select	c.-39G>T		5_prime_UTR	Exon 1 of 3	ENSP00000215565.1
	NDUFB7	ENST00000593353.5	TSL:2	n.-39G>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000473120.1
	NDUFB7	ENST00000593353.5	TSL:2	n.-39G>T		5_prime_UTR	Exon 1 of 3	ENSP00000473120.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000226 AC: 3 AN: 1325476 Hom.: 0 Cov.: 21 AF XY: 0.00000458 AC XY: 3 AN XY: 654844

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30018

American (AMR) AF: 0.00 AC: 0 AN: 33798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23090

East Asian (EAS) AF: 0.00 AC: 0 AN: 36184

South Asian (SAS) AF: 0.0000393 AC: 3 AN: 76356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5146

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1019044

Other (OTH) AF: 0.00 AC: 0 AN: 55164

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Benign	0.83
PhyloP100		2.6
PromoterAI		0.10	Neutral

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: rs45628939; hg19: chr19-14682851;