NM_153271.2:c.400G>A

Variant names:

• chr15-75649502-G-A
• rs372555211
• NM_153271.2:c.400G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153271.2(SNX33):​c.400G>A​(p.Gly134Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 1,563,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G134A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SNX33 NM_153271.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56
• Publications: 0 publications found

Genes affected

SNX33 (HGNC:28468): (sorting nexin 33) The protein encoded by this gene is involved in cytoskeletal reorganization, vesicle trafficking, endocytosis, and mitosis. The encoded protein is essential for the creation of the cleavage furrow during mitosis and for completion of mitosis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11578485).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153271.2. 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
	SNX33	NM_153271.2	MANE Select	c.400G>A	p.Gly134Arg	missense	Exon 1 of 2	NP_695003.1	Q8WV41
	SNX33	NM_001318146.1		c.400G>A	p.Gly134Arg	missense	Exon 1 of 3	NP_001305075.1	Q8WV41

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX33	ENST00000308527.6	TSL:1 MANE Select	c.400G>A	p.Gly134Arg	missense	Exon 1 of 2	ENSP00000311427.6	Q8WV41

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000919 AC: 2 AN: 217706 AF XY: 0.00000856

Gnomad AFR exome AF: 0.00

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: 0.0000200

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1411634 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 695760

African (AFR) AF: 0.00 AC: 0 AN: 32320

American (AMR) AF: 0.00 AC: 0 AN: 38966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39014

South Asian (SAS) AF: 0.00 AC: 0 AN: 79568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5544

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1083456

Other (OTH) AF: 0.00 AC: 0 AN: 58144

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

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	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.6
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.027
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.11	T
Polyphen		0.23	B
Vest4		0.067
MutPred		0.28		Gain of methylation at G134 (P = 0.0144)
MVP		0.68
MPC		0.79
ClinPred		0.22	T
GERP RS		3.7
PromoterAI		0.020	Neutral
Varity_R		0.075
gMVP		0.37

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: rs372555211; hg19: chr15-75941843;