15-40739577-G-A

Position:

• chr15-40739577-G-A

Variant summary

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

The NM_018145.3(RMDN3):​c.971+556C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,716 control chromosomes in the GnomAD database, including 20,309 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 0.51 (20188 hom., cov: 31)
  • Exomes 𝑓: 0.51 (121 hom.)
• Consequence: RMDN3 NM_018145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286

Genes affected

RMDN3 (HGNC:25550): (regulator of microtubule dynamics 3) Enables microtubule binding activity. Involved in cellular calcium ion homeostasis. Located in several cellular components, including intercellular bridge; mitochondrial outer membrane; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

RMDN3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMDN3	NM_018145.3	c.971+556C>T		intron_variant		ENST00000338376.8	NP_060615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMDN3	ENST00000338376.8	c.971+556C>T		intron_variant		1	NM_018145.3	ENSP00000342493.3
RMDN3	ENST00000558777.5	n.*522+556C>T		intron_variant		2		ENSP00000453357.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76870 AN: 151784 Hom.: 20169 Cov.: 31

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.507 AC: 413 AN: 814 Hom.: 121 Cov.: 0 AF XY: 0.519 AC XY: 242 AN XY: 466

Gnomad4 AMR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.929

Gnomad4 SAS exome AF: 0.519

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.471

Gnomad4 OTH exome AF: 0.421

GnomAD4 genome AF: 0.506 AC: 76918 AN: 151902 Hom.: 20188 Cov.: 31 AF XY: 0.517 AC XY: 38361 AN XY: 74220

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.504

Alfa AF: 0.396 Hom.: 1195

Bravo AF: 0.507

Asia WGS AF: 0.713 AC: 2479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.80

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: rs3092983; hg19: chr15-41031775;