chr14-71588038-C-A

Variant names:

• chr14-71588038-C-A
• rs12884638
• NM_001386936.1:c.166C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001386936.1(SIPA1L1):​c.166C>A​(p.Pro56Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0111 in 1,613,896 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (6 hom., cov: 32)
  • Exomes 𝑓: 0.011 (111 hom.)
• Consequence: SIPA1L1 NM_001386936.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.98
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050117075).
• BP6: Variant 14-71588038-C-A is Benign according to our data. Variant chr14-71588038-C-A is described in ClinVar as Benign. ClinVar VariationId is 773722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 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.166C>A	p.Pro56Thr	missense	Exon 5 of 24	NP_001373865.1	O43166-2
	SIPA1L1	NM_001354285.2		c.166C>A	p.Pro56Thr	missense	Exon 5 of 25	NP_001341214.1	O43166-1
	SIPA1L1	NM_015556.4		c.166C>A	p.Pro56Thr	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.166C>A	p.Pro56Thr	missense	Exon 5 of 24	ENSP00000370630.3	O43166-2
	SIPA1L1	ENST00000555818.5	TSL:1	c.166C>A	p.Pro56Thr	missense	Exon 2 of 22	ENSP00000450832.1	O43166-1
	SIPA1L1	ENST00000962884.1		c.166C>A	p.Pro56Thr	missense	Exon 4 of 25	ENSP00000632943.1

Frequencies

GnomAD3 genomes AF: 0.00765 AC: 1163 AN: 152040 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.00624

GnomAD2 exomes AF: 0.00791 AC: 1981 AN: 250498 AF XY: 0.00776

Gnomad AFR exome AF: 0.00235

Gnomad AMR exome AF: 0.00255

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.0114

Gnomad NFE exome AF: 0.0129

Gnomad OTH exome AF: 0.00884

GnomAD4 exome AF: 0.0115 AC: 16796 AN: 1461738 Hom.: 111 Cov.: 30 AF XY: 0.0111 AC XY: 8066 AN XY: 727182

African (AFR) AF: 0.00185 AC: 62 AN: 33470

American (AMR) AF: 0.00291 AC: 130 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 11 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.00335 AC: 289 AN: 86258

European-Finnish (FIN) AF: 0.0117 AC: 623 AN: 53414

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.0136 AC: 15155 AN: 1111908

Other (OTH) AF: 0.00843 AC: 509 AN: 60384

GnomAD4 genome AF: 0.00764 AC: 1163 AN: 152158 Hom.: 6 Cov.: 32 AF XY: 0.00777 AC XY: 578 AN XY: 74368

African (AFR) AF: 0.00258 AC: 107 AN: 41522

American (AMR) AF: 0.00353 AC: 54 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00374 AC: 18 AN: 4818

European-Finnish (FIN) AF: 0.0126 AC: 133 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0122 AC: 829 AN: 67992

Other (OTH) AF: 0.00618 AC: 13 AN: 2104

Alfa AF: 0.00970 Hom.: 21

Bravo AF: 0.00680

TwinsUK AF: 0.00971 AC: 36

ALSPAC AF: 0.0140 AC: 54

ESP6500AA AF: 0.00409 AC: 18

ESP6500EA AF: 0.0110 AC: 95

ExAC AF: 0.00745 AC: 905

Asia WGS AF: 0.00144 AC: 5 AN: 3476

EpiCase AF: 0.0112

EpiControl AF: 0.0114

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.0
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.38
Sift	Benign	0.046	D
Sift4G	Uncertain	0.041	D
Polyphen		0.011	B
Vest4		0.40
MVP		0.43
MPC		0.47
ClinPred		0.0080	T
GERP RS		5.5
Varity_R		0.076
gMVP		0.41
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: rs12884638; hg19: chr14-72054755;