chr1-232402443-T-G

Position:

• chr1-232402443-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020808.5(SIPA1L2):​c.4971A>C​(p.Lys1657Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SIPA1L2 NM_020808.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L2	NM_020808.5	c.4971A>C	p.Lys1657Asn	missense_variant	22/23	ENST00000674635.1	NP_065859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIPA1L2	ENST00000674635.1	c.4971A>C	p.Lys1657Asn	missense_variant	22/23		NM_020808.5	ENSP00000502693	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2023

The c.4971A>C (p.K1657N) alteration is located in exon 20 (coding exon 20) of the SIPA1L2 gene. This alteration results from a A to C substitution at nucleotide position 4971, causing the lysine (K) at amino acid position 1657 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T;.
Eigen	Benign	0.042
Eigen_PC	Benign	-0.094
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	.;D;D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.7	M;M;.
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.80
MutPred		0.32		Loss of ubiquitination at K1657 (P = 0.0071);Loss of ubiquitination at K1657 (P = 0.0071);.;
MVP		0.37
MPC		0.77
ClinPred		0.97	D
GERP RS		0.65
Varity_R		0.60
gMVP		0.53

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: chr1-232538189;