rs139188415

Variant names:

• chr14-71587889-G-A
• rs139188415
• NM_001386936.1:c.17G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-71587889-G-A
• chr14-71587889-G-C
• chr14-71587889-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001386936.1(SIPA1L1):​c.17G>A​(p.Arg6Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000023 in 1,607,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R6W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SIPA1L1 NM_001386936.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.77
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3183946).

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.17G>A	p.Arg6Gln	missense	Exon 5 of 24	NP_001373865.1	O43166-2
	SIPA1L1	NM_001354285.2		c.17G>A	p.Arg6Gln	missense	Exon 5 of 25	NP_001341214.1	O43166-1
	SIPA1L1	NM_015556.4		c.17G>A	p.Arg6Gln	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.17G>A	p.Arg6Gln	missense	Exon 5 of 24	ENSP00000370630.3	O43166-2
	SIPA1L1	ENST00000555818.5	TSL:1	c.17G>A	p.Arg6Gln	missense	Exon 2 of 22	ENSP00000450832.1	O43166-1
	SIPA1L1	ENST00000962884.1		c.17G>A	p.Arg6Gln	missense	Exon 4 of 25	ENSP00000632943.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 250442 AF XY: 0.0000222

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1455380 Hom.: 0 Cov.: 30 AF XY: 0.0000152 AC XY: 11 AN XY: 722476

African (AFR) AF: 0.000360 AC: 12 AN: 33346

American (AMR) AF: 0.00 AC: 0 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000452 AC: 5 AN: 1106526

Other (OTH) AF: 0.0000333 AC: 2 AN: 60088

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74344

African (AFR) AF: 0.000410 AC: 17 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.000147

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

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	Pathogenic	0.80
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.28
Sift	Benign	0.32	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.43	B
Vest4		0.35
MVP		0.66
MPC		1.2
ClinPred		0.78	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.46
Mutation Taster		=81/19	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

dbSNP: rs139188415; hg19: chr14-72054606; COSMIC: COSV62168908; COSMIC: COSV62168908;