15-40739940-A-G

Variant names:

• chr15-40739940-A-G
• rs2304583
• NM_018145.3:c.971+193T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018145.3(RMDN3):​c.971+193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,094 control chromosomes in the GnomAD database, including 6,505 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 0.27 (6505 hom., cov: 32)
• Consequence: RMDN3 NM_018145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 16 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMDN3	NM_018145.3	c.971+193T>C		intron_variant	Intron 7 of 12	ENST00000338376.8	NP_060615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMDN3	ENST00000338376.8	c.971+193T>C		intron_variant	Intron 7 of 12	1	NM_018145.3	ENSP00000342493.3
RMDN3	ENST00000558777.5	n.*522+193T>C		intron_variant	Intron 8 of 13	2		ENSP00000453357.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41118 AN: 151976 Hom.: 6501 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.270 AC: 41129 AN: 152094 Hom.: 6505 Cov.: 32 AF XY: 0.275 AC XY: 20428 AN XY: 74320

African (AFR) AF: 0.123 AC: 5100 AN: 41520

American (AMR) AF: 0.251 AC: 3835 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1237 AN: 3472

East Asian (EAS) AF: 0.105 AC: 544 AN: 5176

South Asian (SAS) AF: 0.343 AC: 1652 AN: 4816

European-Finnish (FIN) AF: 0.430 AC: 4546 AN: 10560

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.344 AC: 23349 AN: 67970

Other (OTH) AF: 0.269 AC: 567 AN: 2110

Alfa AF: 0.310 Hom.: 9784

Bravo AF: 0.245

Asia WGS AF: 0.259 AC: 901 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	4.9
DANN	Benign	0.67
PhyloP100		0.0050
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: rs2304583; hg19: chr15-41032138; COSMIC: COSV53025063; COSMIC: COSV53025063;