NM_152760.3:c.646G>A

Variant names:

• chr11-65851097-G-A
• NM_152760.3:c.646G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152760.3(SNX32):​c.646G>A​(p.Glu216Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SNX32 NM_152760.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.52
• Publications: 0 publications found

Genes affected

SNX32 (HGNC:26423): (sorting nexin 32) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in retrograde transport, endosome to Golgi. Predicted to be located in cytosol. Predicted to be active in endosome. [provided by Alliance of Genome Resources, Apr 2022]

CFL1 (HGNC:1874): (cofilin 1) The protein encoded by this gene can polymerize and depolymerize F-actin and G-actin in a pH-dependent manner. Increased phosphorylation of this protein by LIM kinase aids in Rho-induced reorganization of the actin cytoskeleton. Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. It is involved in the translocation of actin-cofilin complex from cytoplasm to nucleus.[supplied by OMIM, Apr 2004]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152760.3. 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
	SNX32	NM_152760.3	MANE Select	c.646G>A	p.Glu216Lys	missense	Exon 7 of 13	NP_689973.2	Q86XE0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX32	ENST00000308342.7	TSL:1 MANE Select	c.646G>A	p.Glu216Lys	missense	Exon 7 of 13	ENSP00000310620.6	Q86XE0-1
	SNX32	ENST00000526972.5	TSL:1	n.989G>A		non_coding_transcript_exon	Exon 5 of 5
	SNX32	ENST00000946610.1		c.643G>A	p.Glu215Lys	missense	Exon 7 of 13	ENSP00000616669.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461694 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727176

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	0.68
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0066	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.14
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.049	D
Polyphen		0.34	B
Vest4		0.66
MutPred		0.53		Gain of MoRF binding (P = 0.0064)
MVP		0.26
MPC		0.33
ClinPred		0.96	D
GERP RS		2.9
Varity_R		0.29
gMVP		0.16
Mutation Taster		=84/16	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

hg19: chr11-65618568;