17-18009743-T-C

Position:

• chr17-18009743-T-C

Variant summary

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

The NM_031294.4(DRC3):​c.1326+2596T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,028 control chromosomes in the GnomAD database, including 15,121 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 0.43 (15121 hom., cov: 32)
• Consequence: DRC3 NM_031294.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

Genes affected

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

DRC3 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRC3	NM_031294.4	c.1326+2596T>C		intron_variant		ENST00000399187.6	NP_112584.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRC3	ENST00000399187.6	c.1326+2596T>C		intron_variant		1	NM_031294.4	ENSP00000382140.1
DRC3	ENST00000583171.5	n.*418+2596T>C		intron_variant		3		ENSP00000464101.2
DRC3	ENST00000490517.5	n.5371+2596T>C		intron_variant		2
ATPAF2	ENST00000584205.5	n.*33+14881A>G		intron_variant		2		ENSP00000462899.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64664 AN: 151910 Hom.: 15106 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.421

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.426 AC: 64713 AN: 152028 Hom.: 15121 Cov.: 32 AF XY: 0.439 AC XY: 32604 AN XY: 74318

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.421

Alfa AF: 0.392 Hom.: 2586

Bravo AF: 0.434

Asia WGS AF: 0.725 AC: 2519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.83

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: rs6502632; hg19: chr17-17913057;