rs768457830

Variant names:

• chr1-232415578-C-G
• rs768457830
• NM_020808.5:c.4678G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-232415578-C-G
• chr1-232415578-C-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.4678G>C​(p.Ala1560Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A1560T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SIPA1L2 NM_020808.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 4 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=0.110233605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1L2	NM_020808.5	c.4678G>C	p.Ala1560Pro	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.4678G>C	p.Ala1560Pro	missense_variant	Exon 19 of 23		NM_020808.5	ENSP00000502693.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249108 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461600 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727088

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111874

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0087	T;T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.090	N;N;.
PhyloP100		1.8
PrimateAI	Benign	0.47	T
PROVEAN	Benign	3.0	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.41	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.71	P;P;P
Vest4		0.42
MutPred		0.15		Gain of disorder (P = 0.0544);Gain of disorder (P = 0.0544);.;
MVP		0.18
MPC		0.51
ClinPred		0.55	D
GERP RS		-0.37
Varity_R		0.073
gMVP		0.27
Mutation Taster		=85/15	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: rs768457830; hg19: chr1-232551324;