rs61729754

Variant names:

• chr1-232428542-T-G
• rs61729754
• NM_020808.5:c.4279A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-232428542-T-G
• chr1-232428542-T-A

Variant summary

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

The NM_020808.5(SIPA1L2):​c.4279A>C​(p.Met1427Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00767 in 1,585,292 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0079 (67 hom.)
• Consequence: SIPA1L2 NM_020808.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0920
• Publications: 14 publications found

Genes affected

SIPA1L2 (HGNC:23800): (signal induced proliferation associated 1 like 2) This gene encodes a member of the signal-induced proliferation-associated 1 like family. Members of this family contain a GTPase activating domain, a PDZ domain and a C-terminal coiled-coil domain with a leucine zipper. A similar protein in rat acts as a GTPases for the small GTPase Rap. [provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005518347).
• BP6: Variant 1-232428542-T-G is Benign according to our data. Variant chr1-232428542-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2640082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020808.5. 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
	SIPA1L2	NM_020808.5	MANE Select	c.4279A>C	p.Met1427Leu	missense	Exon 17 of 23	NP_065859.3	Q9P2F8-1
	SIPA1L2	NM_001377488.1		c.4279A>C	p.Met1427Leu	missense	Exon 17 of 22	NP_001364417.1	A0A6Q8PH54

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1L2	ENST00000674635.1	MANE Select	c.4279A>C	p.Met1427Leu	missense	Exon 17 of 23	ENSP00000502693.1	Q9P2F8-1
	SIPA1L2	ENST00000676213.1		c.4432A>C	p.Met1478Leu	missense	Exon 17 of 23	ENSP00000501897.1	A0A6Q8PFQ0
	SIPA1L2	ENST00000964479.1		c.4432A>C	p.Met1478Leu	missense	Exon 18 of 24	ENSP00000634538.1

Frequencies

GnomAD3 genomes AF: 0.00572 AC: 870 AN: 152024 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00557

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00932

Gnomad OTH AF: 0.00576

GnomAD2 exomes AF: 0.00580 AC: 1297 AN: 223572 AF XY: 0.00579

Gnomad AFR exome AF: 0.00106

Gnomad AMR exome AF: 0.00352

Gnomad ASJ exome AF: 0.00165

Gnomad EAS exome AF: 0.000126

Gnomad FIN exome AF: 0.00779

Gnomad NFE exome AF: 0.00881

Gnomad OTH exome AF: 0.00803

GnomAD4 exome AF: 0.00788 AC: 11296 AN: 1433150 Hom.: 67 Cov.: 33 AF XY: 0.00779 AC XY: 5547 AN XY: 712206

African (AFR) AF: 0.00145 AC: 46 AN: 31762

American (AMR) AF: 0.00344 AC: 133 AN: 38706

Ashkenazi Jewish (ASJ) AF: 0.00166 AC: 42 AN: 25270

East Asian (EAS) AF: 0.0000522 AC: 2 AN: 38334

South Asian (SAS) AF: 0.00145 AC: 117 AN: 80728

European-Finnish (FIN) AF: 0.00742 AC: 394 AN: 53068

Middle Eastern (MID) AF: 0.00177 AC: 10 AN: 5662

European-Non Finnish (NFE) AF: 0.00918 AC: 10103 AN: 1100462

Other (OTH) AF: 0.00759 AC: 449 AN: 59158

GnomAD4 genome AF: 0.00571 AC: 869 AN: 152142 Hom.: 5 Cov.: 31 AF XY: 0.00544 AC XY: 405 AN XY: 74386

African (AFR) AF: 0.00142 AC: 59 AN: 41528

American (AMR) AF: 0.00582 AC: 89 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00250 AC: 12 AN: 4806

European-Finnish (FIN) AF: 0.00557 AC: 59 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00931 AC: 633 AN: 67984

Other (OTH) AF: 0.00570 AC: 12 AN: 2106

Alfa AF: 0.00772 Hom.: 9

Bravo AF: 0.00511

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.00908 AC: 35

ESP6500AA AF: 0.00361 AC: 14

ESP6500EA AF: 0.00880 AC: 73

ExAC AF: 0.00515 AC: 623

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	0.072
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.6
DANN	Benign	0.38
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.092
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.074
Sift	Benign	0.31	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.085
MutPred		0.24		Loss of disorder (P = 0.0664)
MVP		0.068
MPC		0.16
ClinPred		0.0027	T
GERP RS		-2.9
Varity_R		0.078
gMVP		0.15
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs61729754; hg19: chr1-232564288; COSMIC: COSV99035439;