chr19-8311547-G-A

Position:

• chr19-8311547-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005001.5(NDUFA7):​c.300C>T​(p.Pro100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,611,872 control chromosomes in the GnomAD database, including 27,727 homozygotes. 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: 𝑓 0.16 (2232 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25495 hom.)
• Consequence: NDUFA7 NM_005001.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

NDUFA7 (HGNC:7691): (NADH:ubiquinone oxidoreductase subunit A7) This gene encodes a subunit of NADH:ubiquinone oxidoreductase (complex I), which is a multiprotein complex located in the inner mitochondrial membrane. Complex I functions in the transfer of electrons from NADH to the respiratory chain. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-1.33 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA7	NM_005001.5	c.300C>T	p.Pro100=	synonymous_variant	4/4	ENST00000301457.3	NP_004992.2
NDUFA7	NR_135539.2	n.317C>T		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA7	ENST00000301457.3	c.300C>T	p.Pro100=	synonymous_variant	4/4	1	NM_005001.5	ENSP00000301457	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23679 AN: 152066 Hom.: 2233 Cov.: 32

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.0758

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.195

GnomAD3 exomes AF: 0.181 AC: 44832 AN: 247198 Hom.: 4863 AF XY: 0.173 AC XY: 23170 AN XY: 134276

Gnomad AFR exome AF: 0.0433

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.191

Gnomad EAS exome AF: 0.214

Gnomad SAS exome AF: 0.0655

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.181 AC: 264190 AN: 1459688 Hom.: 25495 Cov.: 31 AF XY: 0.177 AC XY: 128717 AN XY: 726098

Gnomad4 AFR exome AF: 0.0428

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.0671

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.156 AC: 23676 AN: 152184 Hom.: 2232 Cov.: 32 AF XY: 0.155 AC XY: 11566 AN XY: 74396

Gnomad4 AFR AF: 0.0510

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.0750

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.193

Alfa AF: 0.178 Hom.: 5709

Bravo AF: 0.158

Asia WGS AF: 0.155 AC: 542 AN: 3478

EpiCase AF: 0.180

EpiControl AF: 0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.7
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs561; hg19: chr19-8376431; COSMIC: COSV56846606; COSMIC: COSV56846606;