NM_018145.3:c.1349T>G

Variant names:

• chr15-40737134-A-C
• rs1897084771
• NM_018145.3:c.1349T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018145.3(RMDN3):​c.1349T>G​(p.Val450Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V450V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RMDN3 NM_018145.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15003878).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018145.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMDN3	NM_018145.3	MANE Select	c.1349T>G	p.Val450Gly	missense	Exon 12 of 13	NP_060615.1	Q96TC7-1
	RMDN3	NM_001323896.2		c.1427T>G	p.Val476Gly	missense	Exon 12 of 13	NP_001310825.1
	RMDN3	NM_001323897.2		c.1427T>G	p.Val476Gly	missense	Exon 12 of 13	NP_001310826.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMDN3	ENST00000338376.8	TSL:1 MANE Select	c.1349T>G	p.Val450Gly	missense	Exon 12 of 13	ENSP00000342493.3	Q96TC7-1
	RMDN3	ENST00000260385.10	TSL:1	c.1349T>G	p.Val450Gly	missense	Exon 11 of 12	ENSP00000260385.6	Q96TC7-1
	RMDN3	ENST00000558777.5	TSL:2	n.*900T>G		non_coding_transcript_exon	Exon 13 of 14	ENSP00000453357.1	H0YLV7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461804 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727192

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111932

Other (OTH) AF: 0.00 AC: 0 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.022
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.5
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.10
Sift	Benign	0.11	T
Sift4G	Benign	0.30	T
Polyphen		0.0040	B
Vest4		0.24
MutPred		0.51		Loss of stability (P = 0.0012)
MVP		0.32
MPC		0.21
ClinPred		0.27	T
GERP RS		5.8
Varity_R		0.33
gMVP		0.39
Mutation Taster		=78/22	polymorphism

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: rs1897084771; hg19: chr15-41029332;