NM_001386936.1:c.437C>G

Variant names:

• chr14-71588309-C-G
• NM_001386936.1:c.437C>G

Variant summary

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

The NM_001386936.1(SIPA1L1):​c.437C>G​(p.Ser146Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SIPA1L1 NM_001386936.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27853644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1L1	NM_001386936.1	c.437C>G	p.Ser146Trp	missense_variant	Exon 5 of 24	ENST00000381232.8	NP_001373865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1L1	ENST00000381232.8	c.437C>G	p.Ser146Trp	missense_variant	Exon 5 of 24	1	NM_001386936.1	ENSP00000370630.3
SIPA1L1	ENST00000555818.5	c.437C>G	p.Ser146Trp	missense_variant	Exon 2 of 22	1		ENSP00000450832.1
SIPA1L1	ENST00000358550.6	c.437C>G	p.Ser146Trp	missense_variant	Exon 2 of 21	2		ENSP00000351352.2
ENSG00000285612	ENST00000647653.1	n.1053G>C		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461500 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727096

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	.;T;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0090	D;D;D
Sift4G	Benign	0.15	T;T;T
Polyphen		0.95	P;P;.
Vest4		0.42
MutPred		0.34		Gain of catalytic residue at S146 (P = 0.0049);Gain of catalytic residue at S146 (P = 0.0049);Gain of catalytic residue at S146 (P = 0.0049);
MVP		0.63
MPC		0.75
ClinPred		0.68	D
GERP RS		4.6
Varity_R		0.097
gMVP		0.37

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: chr14-72055026;