15-40752692-T-C

Variant names:

• chr15-40752692-T-C
• rs752012
• NM_018145.3:c.188-514A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RMDN3	NM_018145.3	c.188-514A>G		intron_variant	Intron 2 of 12	ENST00000338376.8	NP_060615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMDN3	ENST00000338376.8	c.188-514A>G		intron_variant	Intron 2 of 12	1	NM_018145.3	ENSP00000342493.3
RMDN3	ENST00000558777.5	n.90-514A>G		intron_variant	Intron 3 of 13	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

African (AFR) AF: 0.519 AC: 21494 AN: 41404

American (AMR) AF: 0.613 AC: 9352 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1954 AN: 3468

East Asian (EAS) AF: 0.773 AC: 3999 AN: 5172

South Asian (SAS) AF: 0.651 AC: 3134 AN: 4816

European-Finnish (FIN) AF: 0.584 AC: 6155 AN: 10540

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33749 AN: 67952

Other (OTH) AF: 0.523 AC: 1101 AN: 2104

Alfa AF: 0.517 Hom.: 55988

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
PhyloP100		-0.084
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs752012; hg19: chr15-41044890;