14-71587991-G-A

Variant names:

• chr14-71587991-G-A
• rs78621209
• NM_001386936.1:c.119G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001386936.1(SIPA1L1):​c.119G>A​(p.Arg40Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0096 in 1,614,038 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R40W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0078 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0098 (91 hom.)
• Consequence: SIPA1L1 NM_001386936.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 8.02
• Publications: 6 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007160008).
• BP6: Variant 14-71587991-G-A is Benign according to our data. Variant chr14-71587991-G-A is described in ClinVar as Benign. ClinVar VariationId is 783046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 9 gene

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.119G>A	p.Arg40Gln	missense	Exon 5 of 24	NP_001373865.1	O43166-2
	SIPA1L1	NM_001354285.2		c.119G>A	p.Arg40Gln	missense	Exon 5 of 25	NP_001341214.1	O43166-1
	SIPA1L1	NM_015556.4		c.119G>A	p.Arg40Gln	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.119G>A	p.Arg40Gln	missense	Exon 5 of 24	ENSP00000370630.3	O43166-2
	SIPA1L1	ENST00000555818.5	TSL:1	c.119G>A	p.Arg40Gln	missense	Exon 2 of 22	ENSP00000450832.1	O43166-1
	SIPA1L1	ENST00000962884.1		c.119G>A	p.Arg40Gln	missense	Exon 4 of 25	ENSP00000632943.1

Frequencies

GnomAD3 genomes AF: 0.00784 AC: 1193 AN: 152118 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00763 AC: 1917 AN: 251128 AF XY: 0.00791

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.00283

Gnomad ASJ exome AF: 0.00467

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0112

Gnomad NFE exome AF: 0.0118

Gnomad OTH exome AF: 0.00734

GnomAD4 exome AF: 0.00979 AC: 14305 AN: 1461802 Hom.: 91 Cov.: 30 AF XY: 0.00969 AC XY: 7046 AN XY: 727208

African (AFR) AF: 0.00137 AC: 46 AN: 33472

American (AMR) AF: 0.00284 AC: 127 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00494 AC: 129 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00413 AC: 356 AN: 86256

European-Finnish (FIN) AF: 0.0101 AC: 540 AN: 53420

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.0113 AC: 12570 AN: 1111948

Other (OTH) AF: 0.00843 AC: 509 AN: 60392

GnomAD4 genome AF: 0.00784 AC: 1193 AN: 152236 Hom.: 9 Cov.: 32 AF XY: 0.00736 AC XY: 548 AN XY: 74428

African (AFR) AF: 0.00154 AC: 64 AN: 41550

American (AMR) AF: 0.00562 AC: 86 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4824

European-Finnish (FIN) AF: 0.0108 AC: 114 AN: 10596

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0123 AC: 836 AN: 68012

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00989 Hom.: 43

Bravo AF: 0.00655

TwinsUK AF: 0.00998 AC: 37

ALSPAC AF: 0.0104 AC: 40

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.0108 AC: 93

ExAC AF: 0.00826 AC: 1003

Asia WGS AF: 0.00231 AC: 8 AN: 3476

EpiCase AF: 0.0139

EpiControl AF: 0.0115

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0072	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.6	L
PhyloP100		8.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.80	N
REVEL	Uncertain	0.37
Sift	Benign	0.28	T
Sift4G	Benign	0.30	T
Polyphen		0.94	P
Vest4		0.54
MVP		0.78
MPC		0.66
ClinPred		0.036	T
GERP RS		5.5
Varity_R		0.20
gMVP		0.51
Mutation Taster		=92/8	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: rs78621209; hg19: chr14-72054708; COSMIC: COSV100666187; COSMIC: COSV100666187;