14-71587889-G-C

Variant names:

• chr14-71587889-G-C
• NM_001386936.1:c.17G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001386936.1(SIPA1L1):​c.17G>C​(p.Arg6Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,380 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SIPA1L1 NM_001386936.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.77

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1L1	NM_001386936.1	c.17G>C	p.Arg6Pro	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.17G>C	p.Arg6Pro	missense_variant	Exon 5 of 24	1	NM_001386936.1	ENSP00000370630.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455380 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722476

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: 0.00

Gnomad4 NFE exome AF: 9.04e-7

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	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.093	T;.;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Uncertain	-0.046	T
MutationAssessor	Benign	0.98	.;L;L;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-7.0	D;N;N;N
REVEL	Uncertain	0.51
Sift	Uncertain	0.0060	.;D;T;D
Sift4G	Pathogenic	0.0	D;T;T;T
Polyphen		0.027, 1.0	.;B;D;.
Vest4		0.36, 0.40, 0.43
MutPred		0.26		Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);
MVP		0.65
MPC		1.3
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.50

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: chr14-72054606;