rs1215432895

Variant names:

• chr1-232415581-A-C
• rs1215432895
• NM_020808.5:c.4675T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-232415581-A-C
• chr1-232415581-A-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.4675T>G​(p.Cys1559Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. C1559S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SIPA1L2 NM_020808.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56
• 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=0.14167061).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1L2	NM_020808.5	c.4675T>G	p.Cys1559Gly	missense_variant	Exon 19 of 23	ENST00000674635.1	NP_065859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1L2	ENST00000674635.1	c.4675T>G	p.Cys1559Gly	missense_variant	Exon 19 of 23		NM_020808.5	ENSP00000502693.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461704 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727152

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111926

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.020	T;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.
PhyloP100		4.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.31	N;N;N
REVEL	Benign	0.023
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.33	T;T;D
Polyphen		0.30	B;B;P
Vest4		0.47
MutPred		0.25		Loss of methylation at K1558 (P = 0.0165);Loss of methylation at K1558 (P = 0.0165);.;
MVP		0.082
MPC		0.42
ClinPred		0.66	D
GERP RS		4.4
Varity_R		0.21
gMVP		0.24
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: rs1215432895; hg19: chr1-232551327;