1-232404131-A-G

Position:

• chr1-232404131-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020808.5(SIPA1L2):​c.4810T>C​(p.Tyr1604His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 6.60

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26528993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L2	NM_020808.5	c.4810T>C	p.Tyr1604His	missense_variant	20/23	ENST00000674635.1	NP_065859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIPA1L2	ENST00000674635.1	c.4810T>C	p.Tyr1604His	missense_variant	20/23		NM_020808.5	ENSP00000502693	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Dec 14, 2021

The c.4810T>C (p.Y1604H) alteration is located in exon 18 (coding exon 18) of the SIPA1L2 gene. This alteration results from a T to C substitution at nucleotide position 4810, causing the tyrosine (Y) at amino acid position 1604 to be replaced by a histidine (H). 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	Benign	0.12
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	.;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	0.96	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.24	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.056	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.91	P;P
Vest4		0.26
MutPred		0.34		Gain of disorder (P = 0.0151);Gain of disorder (P = 0.0151);
MVP		0.15
MPC		0.56
ClinPred		0.75	D
GERP RS		5.4
Varity_R		0.13
gMVP		0.078

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr1-232539877;