rs4368210

chr17-17992776-C-T

Variant summary

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

The NM_031294.4(DRC3):c.456C>T(p.Leu152=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,612,222 control chromosomes in the GnomAD database, including 126,249 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 0.40 (13438 hom., cov: 31)
  • Exomes 𝑓: 0.37 (112811 hom.)
• Consequence: DRC3 NM_031294.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269

Genes affected

DRC3 (HGNC:25384): (dynein regulatory complex subunit 3) Located in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

ATPAF2 (HGNC:18802): (ATP synthase mitochondrial F1 complex assembly factor 2) This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 alpha subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly. This gene is located within the Smith-Magenis syndrome region on chromosome 17. An alternatively spliced transcript variant has been described, but its biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.269 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRC3	NM_031294.4	c.456C>T	p.Leu152=	synonymous_variant	6/14	ENST00000399187.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRC3	ENST00000399187.6	c.456C>T	p.Leu152=	synonymous_variant	6/14	1	NM_031294.4	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61088 AN: 151788 Hom.: 13431 Cov.: 31

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.406

GnomAD3 exomes AF: 0.466 AC: 115311 AN: 247446 Hom.: 30963 AF XY: 0.470 AC XY: 63082 AN XY: 134244

Gnomad AFR exome AF: 0.416

Gnomad AMR exome AF: 0.599

Gnomad ASJ exome AF: 0.413

Gnomad EAS exome AF: 0.880

Gnomad SAS exome AF: 0.711

Gnomad FIN exome AF: 0.381

Gnomad NFE exome AF: 0.323

Gnomad OTH exome AF: 0.424

GnomAD4 exome AF: 0.368 AC: 537321 AN: 1460314 Hom.: 112811 Cov.: 36 AF XY: 0.378 AC XY: 274745 AN XY: 726392

Gnomad4 AFR exome AF: 0.410

Gnomad4 AMR exome AF: 0.587

Gnomad4 ASJ exome AF: 0.415

Gnomad4 EAS exome AF: 0.865

Gnomad4 SAS exome AF: 0.706

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.402 AC: 61128 AN: 151908 Hom.: 13438 Cov.: 31 AF XY: 0.416 AC XY: 30868 AN XY: 74234

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.405

Alfa AF: 0.353 Hom.: 12781

Bravo AF: 0.409

Asia WGS AF: 0.704 AC: 2447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	2.1
Dann	Benign	0.66

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: rs4368210; hg19: chr17-17896090; COSMIC: COSV58263374; COSMIC: COSV58263374;