20-45834234-C-T

Variant names:

• chr20-45834234-C-T
• rs1302708117
• NM_033421.4:c.55C>T

Variant summary

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

The NM_033421.4(SNX21):​c.55C>T​(p.Arg19Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000576 in 1,562,136 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SNX21 NM_033421.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38
• Publications: 1 publications found

Genes affected

SNX21 (HGNC:16154): (sorting nexin family member 21) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region, like some family members. The specific function of this protein has not been determined. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

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_033421.4. 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
	SNX21	NM_033421.4	MANE Select	c.55C>T	p.Arg19Trp	missense	Exon 2 of 4	NP_219489.1	Q969T3-1
	SNX21	NM_152897.3		c.55C>T	p.Arg19Trp	missense	Exon 2 of 5	NP_690857.1	Q969T3-2
	SNX21	NM_001042633.3		c.55C>T	p.Arg19Trp	missense	Exon 2 of 5	NP_001036098.1	A0A0S2Z632

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX21	ENST00000491381.6	TSL:1 MANE Select	c.55C>T	p.Arg19Trp	missense	Exon 2 of 4	ENSP00000418593.1	Q969T3-1
	SNX21	ENST00000342644.9	TSL:1	c.55C>T	p.Arg19Trp	missense	Exon 2 of 5	ENSP00000344586.5	Q969T3-2
	SNX21	ENST00000462307.5	TSL:1	c.55C>T	p.Arg19Trp	missense	Exon 2 of 5	ENSP00000420169.1	Q969T3-3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000355 AC: 5 AN: 1409940 Hom.: 0 Cov.: 31 AF XY: 0.00000286 AC XY: 2 AN XY: 698408

African (AFR) AF: 0.00 AC: 0 AN: 32480

American (AMR) AF: 0.00 AC: 0 AN: 38758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24226

East Asian (EAS) AF: 0.00 AC: 0 AN: 38698

South Asian (SAS) AF: 0.00 AC: 0 AN: 80800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5528

European-Non Finnish (NFE) AF: 0.00000457 AC: 5 AN: 1094108

Other (OTH) AF: 0.00 AC: 0 AN: 58418

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.33	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.4
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.19
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.49		Gain of catalytic residue at R19 (P = 0.0432)
MVP		0.59
MPC		0.66
ClinPred		1.0	D
GERP RS		4.8
PromoterAI		0.064	Neutral
Varity_R		0.24
gMVP		0.30
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1302708117; hg19: chr20-44462873;