rs759329797

Variant names:

• chr8-86508565-G-A
• rs759329797
• NM_016033.3:c.56C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-86508565-G-A
• chr8-86508565-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016033.3(RMDN1):​c.56C>T​(p.Pro19Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,600,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: RMDN1 NM_016033.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.10
• Publications: 0 publications found

Genes affected

RMDN1 (HGNC:24285): (regulator of microtubule dynamics 1) Enables microtubule binding activity. Predicted to be involved in attachment of mitotic spindle microtubules to kinetochore and mitotic spindle organization. Located in mitotic spindle pole and spindle microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049004942).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016033.3. 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
	RMDN1	NM_016033.3	MANE Select	c.56C>T	p.Pro19Leu	missense	Exon 1 of 10	NP_057117.2	Q96DB5-1
	RMDN1	NM_001286719.2		c.56C>T	p.Pro19Leu	missense	Exon 1 of 9	NP_001273648.1	Q96DB5-2
	RMDN1	NM_001286707.2		c.56C>T	p.Pro19Leu	missense	Exon 1 of 9	NP_001273636.1	Q96DB5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMDN1	ENST00000406452.8	TSL:1 MANE Select	c.56C>T	p.Pro19Leu	missense	Exon 1 of 10	ENSP00000385927.3	Q96DB5-1
	RMDN1	ENST00000902721.1		c.56C>T	p.Pro19Leu	missense	Exon 1 of 11	ENSP00000572780.1
	RMDN1	ENST00000902719.1		c.56C>T	p.Pro19Leu	missense	Exon 1 of 10	ENSP00000572778.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00 AC: 0 AN: 226894 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1448662 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 719832

African (AFR) AF: 0.00 AC: 0 AN: 33306

American (AMR) AF: 0.0000689 AC: 3 AN: 43572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39236

South Asian (SAS) AF: 0.00 AC: 0 AN: 84754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5466

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107642

Other (OTH) AF: 0.0000167 AC: 1 AN: 59846

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74382

African (AFR) AF: 0.000121 AC: 5 AN: 41468

American (AMR) AF: 0.000458 AC: 7 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000958 AC: 2 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000151

ClinVar

ClinVar submissions as Germline

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	0.094
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.22
DANN	Benign	0.94
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		-1.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.0030
Sift	Benign	0.10	T
Sift4G	Benign	0.34	T
Polyphen		0.16	B
Vest4		0.12
MutPred		0.23		Loss of loop (P = 0.0022)
MVP		0.13
MPC		0.062
ClinPred		0.073	T
GERP RS		-6.2
PromoterAI		-0.0047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.024
gMVP		0.37
Mutation Taster		=99/1	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: rs759329797; hg19: chr8-87520794;