19-54103097-T-C

Position:

• chr19-54103097-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004542.4(NDUFA3):​c.11-17T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,608,196 control chromosomes in the GnomAD database, including 254,784 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 0.56 (23745 hom., cov: 30)
  • Exomes 𝑓: 0.56 (231039 hom.)
• Consequence: NDUFA3 NM_004542.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

Genes affected

NDUFA3 (HGNC:7686): (NADH:ubiquinone oxidoreductase subunit A3) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion. Part of mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA3	NM_004542.4	c.11-17T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000485876.6	NP_004533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA3	ENST00000485876.6	c.11-17T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004542.4	ENSP00000418438	P1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84284 AN: 151602 Hom.: 23734 Cov.: 30

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.531

GnomAD3 exomes AF: 0.516 AC: 125833 AN: 243980 Hom.: 33391 AF XY: 0.519 AC XY: 68475 AN XY: 131820

Gnomad AFR exome AF: 0.602

Gnomad AMR exome AF: 0.336

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.472

Gnomad SAS exome AF: 0.490

Gnomad FIN exome AF: 0.526

Gnomad NFE exome AF: 0.571

Gnomad OTH exome AF: 0.524

GnomAD4 exome AF: 0.560 AC: 816312 AN: 1456476 Hom.: 231039 Cov.: 38 AF XY: 0.559 AC XY: 405074 AN XY: 724088

Gnomad4 AFR exome AF: 0.609

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.511

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.531

Gnomad4 NFE exome AF: 0.580

Gnomad4 OTH exome AF: 0.549

GnomAD4 genome AF: 0.556 AC: 84334 AN: 151720 Hom.: 23745 Cov.: 30 AF XY: 0.549 AC XY: 40681 AN XY: 74150

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.530

Alfa AF: 0.564 Hom.: 45812

Bravo AF: 0.551

Asia WGS AF: 0.497 AC: 1730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs254259; hg19: chr19-54606405; COSMIC: COSV52927611; COSMIC: COSV52927611;