chr1-232428492-C-G

Variant names:

• chr1-232428492-C-G
• rs1437275578
• NM_020808.5:c.4329G>C

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.4329G>C​(p.Glu1443Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,108 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SIPA1L2 NM_020808.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.876
• 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=0.25016624).

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.4329G>C	p.Glu1443Asp	missense	Exon 17 of 23	NP_065859.3	Q9P2F8-1
	SIPA1L2	NM_001377488.1		c.4329G>C	p.Glu1443Asp	missense	Exon 17 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.4329G>C	p.Glu1443Asp	missense	Exon 17 of 23	ENSP00000502693.1	Q9P2F8-1
	SIPA1L2	ENST00000676213.1		c.4482G>C	p.Glu1494Asp	missense	Exon 17 of 23	ENSP00000501897.1	A0A6Q8PFQ0
	SIPA1L2	ENST00000964479.1		c.4482G>C	p.Glu1494Asp	missense	Exon 18 of 24	ENSP00000634538.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000418 AC: 1 AN: 239256 AF XY: 0.00000770

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: 0.00000138 AC: 2 AN: 1450108 Hom.: 0 Cov.: 33 AF XY: 0.00000277 AC XY: 2 AN XY: 721098

African (AFR) AF: 0.00 AC: 0 AN: 32772

American (AMR) AF: 0.00 AC: 0 AN: 42606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 38914

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 83898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106938

Other (OTH) AF: 0.0000167 AC: 1 AN: 59934

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.88
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.16
Sift	Benign	0.44	T
Sift4G	Benign	0.56	T
Polyphen		0.87	P
Vest4		0.082
MutPred		0.70		Loss of stability (P = 0.1807)
MVP		0.19
MPC		0.16
ClinPred		0.22	T
GERP RS		1.9
Varity_R		0.042
gMVP		0.15
Mutation Taster		=84/16	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: rs1437275578; hg19: chr1-232564238;