14-71588023-A-T

Position:

• chr14-71588023-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L1	NM_001386936.1	c.151A>T	p.Met51Leu	missense_variant	5/24	ENST00000381232.8	NP_001373865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIPA1L1	ENST00000381232.8	c.151A>T	p.Met51Leu	missense_variant	5/24	1	NM_001386936.1	ENSP00000370630.3
SIPA1L1	ENST00000555818.5	c.151A>T	p.Met51Leu	missense_variant	2/22	1		ENSP00000450832.1
SIPA1L1	ENST00000358550.6	c.151A>T	p.Met51Leu	missense_variant	2/21	2		ENSP00000351352.2
ENSG00000285612	ENST00000647653.1	n.1339T>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jul 15, 2024

The c.151A>T (p.M51L) alteration is located in exon 2 (coding exon 1) of the SIPA1L1 gene. This alteration results from a A to T substitution at nucleotide position 151, causing the methionine (M) at amino acid position 51 to be replaced by a leucine (L). 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	0.082
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;T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.46	N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.43	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.57	T;T;T
Sift4G	Benign	0.83	T;T;T
Polyphen		0.37	B;P;.
Vest4		0.24
MutPred		0.23		Loss of MoRF binding (P = 0.0797);Loss of MoRF binding (P = 0.0797);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

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: chr14-72054740;