chr12-123430644-T-G

Variant names:

• chr12-123430644-T-G
• rs1566093209
• NM_145058.3:c.355A>C

Variant summary

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

The NM_145058.3(RILPL2):​c.355A>C​(p.Asn119His) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N119D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RILPL2 NM_145058.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 0 publications found

Genes affected

RILPL2 (HGNC:28787): (Rab interacting lysosomal protein like 2) This gene encodes a protein that contains a rab-interacting lysosomal protein-like domain. This protein may be involved in regulating lysosome morphology. This protein may also be a target for the Hepatitis C virus and assist in viral replication. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

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=0.24486375).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145058.3. 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
	RILPL2	NM_145058.3	MANE Select	c.355A>C	p.Asn119His	missense	Exon 2 of 4	NP_659495.1	Q969X0
	RILPL2	NR_130703.2		n.603+5438A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RILPL2	ENST00000280571.10	TSL:1 MANE Select	c.355A>C	p.Asn119His	missense	Exon 2 of 4	ENSP00000280571.8	Q969X0
	RILPL2	ENST00000718483.1		c.355A>C	p.Asn119His	missense	Exon 2 of 4	ENSP00000520843.1	A0ABB0MVJ7
	RILPL2	ENST00000718482.1		c.355A>C	p.Asn119His	missense	Exon 2 of 4	ENSP00000520842.1	A0ABB0MVH7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.081
Eigen_PC	Benign	-0.050
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.049	D
Polyphen		0.92	P
Vest4		0.30
MutPred		0.082		Gain of catalytic residue at K120 (P = 0.0775)
MVP		0.51
MPC		0.95
ClinPred		0.79	D
GERP RS		3.9
Varity_R		0.12
gMVP		0.20
Mutation Taster		=90/10	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: rs1566093209; hg19: chr12-123915191;