1-232402396-C-A

Variant names:

• chr1-232402396-C-A
• rs200757572
• NM_020808.5:c.5018G>T

Variant summary

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

The NM_020808.5(SIPA1L2):​c.5018G>T​(p.Arg1673Leu) 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. 14/22 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. R1673Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SIPA1L2 NM_020808.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 0 publications found

Genes affected

SIPA1L2 (HGNC:23800): (signal induced proliferation associated 1 like 2) This gene encodes a member of the signal-induced proliferation-associated 1 like family. Members of this family contain a GTPase activating domain, a PDZ domain and a C-terminal coiled-coil domain with a leucine zipper. A similar protein in rat acts as a GTPases for the small GTPase Rap. [provided by RefSeq, Sep 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=0.17629734).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020808.5. 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
	SIPA1L2	NM_020808.5	MANE Select	c.5018G>T	p.Arg1673Leu	missense	Exon 22 of 23	NP_065859.3	Q9P2F8-1
	SIPA1L2	NM_001377488.1		c.4964G>T	p.Arg1655Leu	missense	Exon 21 of 22	NP_001364417.1	A0A6Q8PH54

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1L2	ENST00000674635.1	MANE Select	c.5018G>T	p.Arg1673Leu	missense	Exon 22 of 23	ENSP00000502693.1	Q9P2F8-1
	SIPA1L2	ENST00000676213.1		c.5171G>T	p.Arg1724Leu	missense	Exon 22 of 23	ENSP00000501897.1	A0A6Q8PFQ0
	SIPA1L2	ENST00000964479.1		c.5171G>T	p.Arg1724Leu	missense	Exon 23 of 24	ENSP00000634538.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.082
Sift	Benign	0.21	T
Sift4G	Benign	0.29	T
Polyphen		0.0020	B
Vest4		0.42
MutPred		0.26		Loss of MoRF binding (P = 0.0073)
MVP		0.15
MPC		0.22
ClinPred		0.52	D
GERP RS		2.5
Varity_R		0.094
gMVP		0.34
Mutation Taster		=83/17	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: rs200757572; hg19: chr1-232538142;