chr15-64151822-C-T

Position:

• chr15-64151822-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024798.3(SNX22):​c.47C>T​(p.Pro16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNX22 NM_024798.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98

Genes affected

SNX22 (HGNC:16315): (sorting nexin 22) The protein encoded by this gene is a sorting nexin that is found in the cytoplasm, where it interacts with membrane-bound phosphatidylinositol 3-phosphate. The encoded protein may play a role in intracellular trafficking. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Dec 2012]

SNX22 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX22	NM_024798.3	c.47C>T	p.Pro16Leu	missense_variant	1/7	ENST00000325881.9	NP_079074.2
SNX22	XM_005254677.4	c.47C>T	p.Pro16Leu	missense_variant	1/5		XP_005254734.1
SNX22	XM_017022581.2	c.47C>T	p.Pro16Leu	missense_variant	1/6		XP_016878070.1
SNX22	NR_073534.2	n.92C>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX22	ENST00000325881.9	c.47C>T	p.Pro16Leu	missense_variant	1/7	1	NM_024798.3	ENSP00000323435.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1386166 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 683898

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000113 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.47C>T (p.P16L) alteration is located in exon 1 (coding exon 1) of the SNX22 gene. This alteration results from a C to T substitution at nucleotide position 47, causing the proline (P) at amino acid position 16 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.028
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.88	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.63	T
Polyphen		1.0	D
Vest4		0.22
MutPred		0.43		Loss of glycosylation at P16 (P = 0.0422);
MVP		0.73
MPC		0.37
ClinPred		0.96	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.21
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs775632128; hg19: chr15-64444021;