rs200757572

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-232402396-C-A
• chr1-232402396-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17629734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1L2	NM_020808.5	c.5018G>T	p.Arg1673Leu	missense_variant	Exon 22 of 23	ENST00000674635.1	NP_065859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1L2	ENST00000674635.1	c.5018G>T	p.Arg1673Leu	missense_variant	Exon 22 of 23		NM_020808.5	ENSP00000502693.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.53	.;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.69	N;N;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.5	D;D;D
REVEL	Benign	0.082
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.42
MutPred		0.26		Loss of MoRF binding (P = 0.0073);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-232538142;