chr15-40737469-T-C

Position:

• chr15-40737469-T-C

Variant summary

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

The NM_018145.3(RMDN3):​c.1225-128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,145,010 control chromosomes in the GnomAD database, including 31,774 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 0.18 (3806 hom., cov: 32)
  • Exomes 𝑓: 0.20 (27968 hom.)
• Consequence: RMDN3 NM_018145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.928

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMDN3	NM_018145.3	c.1225-128A>G		intron_variant		ENST00000338376.8	NP_060615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMDN3	ENST00000338376.8	c.1225-128A>G		intron_variant		1	NM_018145.3	ENSP00000342493.3
RMDN3	ENST00000558777.5	n.*776-128A>G		intron_variant		2		ENSP00000453357.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27317 AN: 152028 Hom.: 3799 Cov.: 32

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.201 AC: 199169 AN: 992864 Hom.: 27968 Cov.: 13 AF XY: 0.201 AC XY: 102467 AN XY: 510120

Gnomad4 AFR exome AF: 0.0809

Gnomad4 AMR exome AF: 0.491

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.699

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.180 AC: 27335 AN: 152146 Hom.: 3806 Cov.: 32 AF XY: 0.188 AC XY: 13982 AN XY: 74386

Gnomad4 AFR AF: 0.0854

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.198

Alfa AF: 0.186 Hom.: 7619

Bravo AF: 0.198

Asia WGS AF: 0.460 AC: 1598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.0
DANN	Benign	0.82

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: rs2304580; hg19: chr15-41029667;