14-71588324-C-T

Variant names:

• chr14-71588324-C-T
• NM_001386936.1:c.452C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001386936.1(SIPA1L1):​c.452C>T​(p.Ser151Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 32)
• Consequence: SIPA1L1 NM_001386936.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.07
• Publications: 0 publications found

Genes affected

SIPA1L1 (HGNC:20284): (signal induced proliferation associated 1 like 1) Predicted to enable GTPase activator activity; actin filament binding activity; and protein kinase binding activity. Predicted to be involved in several processes, including actin cytoskeleton organization; activation of GTPase activity; and regulation of postsynapse organization. Located in actin cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285612 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26579964).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386936.1. 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
	SIPA1L1	NM_001386936.1	MANE Select	c.452C>T	p.Ser151Phe	missense	Exon 5 of 24	NP_001373865.1	O43166-2
	SIPA1L1	NM_001354285.2		c.452C>T	p.Ser151Phe	missense	Exon 5 of 25	NP_001341214.1	O43166-1
	SIPA1L1	NM_015556.4		c.452C>T	p.Ser151Phe	missense	Exon 7 of 27	NP_056371.1	O43166-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1L1	ENST00000381232.8	TSL:1 MANE Select	c.452C>T	p.Ser151Phe	missense	Exon 5 of 24	ENSP00000370630.3	O43166-2
	SIPA1L1	ENST00000555818.5	TSL:1	c.452C>T	p.Ser151Phe	missense	Exon 2 of 22	ENSP00000450832.1	O43166-1
	SIPA1L1	ENST00000962884.1		c.452C>T	p.Ser151Phe	missense	Exon 4 of 25	ENSP00000632943.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.32
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.27	T
MetaSVM	Uncertain	0.068	D
MutationAssessor	Benign	0.66	N
PhyloP100		2.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.011	D
Sift4G	Benign	0.068	T
Polyphen		0.99	D
Vest4		0.27
MutPred		0.40		Gain of sheet (P = 0.0028)
MVP		0.43
MPC		0.87
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.20
gMVP		0.35
Mutation Taster		=76/24	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

hg19: chr14-72055041;