14-71588023-A-T

Variant names:

• chr14-71588023-A-T
• NM_001386936.1:c.151A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001386936.1(SIPA1L1):​c.151A>T​(p.Met51Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M51V) has been classified 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: 2.36
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10282028).

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.151A>T	p.Met51Leu	missense	Exon 5 of 24	NP_001373865.1	O43166-2
	SIPA1L1	NM_001354285.2		c.151A>T	p.Met51Leu	missense	Exon 5 of 25	NP_001341214.1	O43166-1
	SIPA1L1	NM_015556.4		c.151A>T	p.Met51Leu	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.151A>T	p.Met51Leu	missense	Exon 5 of 24	ENSP00000370630.3	O43166-2
	SIPA1L1	ENST00000555818.5	TSL:1	c.151A>T	p.Met51Leu	missense	Exon 2 of 22	ENSP00000450832.1	O43166-1
	SIPA1L1	ENST00000962884.1		c.151A>T	p.Met51Leu	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	0.082
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Benign	0.37
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.46	N
PhyloP100		2.4
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.18
Sift	Benign	0.57	T
Sift4G	Benign	0.83	T
Polyphen		0.37	B
Vest4		0.24
MutPred		0.23		Loss of MoRF binding (P = 0.0797)
MVP		0.36
MPC		0.31
ClinPred		0.21	T
GERP RS		4.3
Varity_R		0.083
gMVP		0.092
Mutation Taster		=96/4	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: chr14-72054740;