NM_203400.5:c.31T>G

Variant names:

• chr17-46978977-A-C
• rs2091469502
• NM_203400.5:c.31T>G

Variant summary

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

The NM_203400.5(RPRML):​c.31T>G​(p.Leu11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPRML NM_203400.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0190
• Publications: 0 publications found

Genes affected

RPRML (HGNC:32422): (reprimo like) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000262633 (HGNC:):

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [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=0.08137846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203400.5. 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
	RPRML	NM_203400.5	MANE Select	c.31T>G	p.Leu11Val	missense	Exon 1 of 1	NP_981945.1	Q8N4K4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPRML	ENST00000322329.5	TSL:6 MANE Select	c.31T>G	p.Leu11Val	missense	Exon 1 of 1	ENSP00000318032.3	Q8N4K4
	ENSG00000262633	ENST00000571841.1	TSL:5	n.676+12351A>C		intron	N/A	ENSP00000461460.1	E7EQ34
	ENSG00000291209	ENST00000570478.6	TSL:4	n.291+206A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1296316 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 638910

African (AFR) AF: 0.00 AC: 0 AN: 25198

American (AMR) AF: 0.00 AC: 0 AN: 19594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21808

East Asian (EAS) AF: 0.00 AC: 0 AN: 27994

South Asian (SAS) AF: 0.00 AC: 0 AN: 68930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3966

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1042486

Other (OTH) AF: 0.00 AC: 0 AN: 53514

GnomAD4 genome Cov.: 33

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	0.067
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.49	N
PhyloP100		0.019
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.049
Sift	Benign	0.11	T
Sift4G	Benign	0.36	T
Polyphen		0.12	B
Vest4		0.21
MutPred		0.19		Gain of loop (P = 0.0166)
MVP		0.014
MPC		1.3
ClinPred		0.054	T
GERP RS		-1.5
PromoterAI		-0.0062	Neutral
Varity_R		0.053
gMVP		0.14

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: rs2091469502; hg19: chr17-45056343;