chr15-40752692-T-C

Position:

• chr15-40752692-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.188-514A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,908 control chromosomes in the GnomAD database, including 22,232 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 0.54 (22232 hom., cov: 31)
• Consequence: RMDN3 NM_018145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMDN3	NM_018145.3	c.188-514A>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.188-514A>G		intron_variant		1	NM_018145.3	ENSP00000342493.3
RMDN3	ENST00000558777.5	n.90-514A>G		intron_variant		2		ENSP00000453357.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81426 AN: 151790 Hom.: 22207 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.537 AC: 81503 AN: 151908 Hom.: 22232 Cov.: 31 AF XY: 0.545 AC XY: 40486 AN XY: 74242

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.523

Alfa AF: 0.513 Hom.: 34029

Bravo AF: 0.540

Asia WGS AF: 0.717 AC: 2492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.8
DANN	Benign	0.57

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: rs752012; hg19: chr15-41044890;