15-64154504-C-G

Variant names:

• chr15-64154504-C-G
• rs773354511
• NM_024798.3:c.578C>G

Variant summary

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

The NM_024798.3(SNX22):​c.578C>G​(p.Pro193Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P193L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX22 NM_024798.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 1 publications found

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]

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=0.16237468).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024798.3. 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
	SNX22	NM_024798.3	MANE Select	c.578C>G	p.Pro193Arg	missense	Exon 7 of 7	NP_079074.2	Q96L94-1
	SNX22	NR_073534.2		n.670C>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX22	ENST00000325881.9	TSL:1 MANE Select	c.578C>G	p.Pro193Arg	missense	Exon 7 of 7	ENSP00000323435.4	Q96L94-1
	SNX22	ENST00000560945.1	TSL:1	n.1697C>G		non_coding_transcript_exon	Exon 4 of 4
	SNX22	ENST00000560997.1	TSL:1	n.391C>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.23	B
Vest4		0.31
MutPred		0.28		Loss of glycosylation at P193 (P = 0.0049)
MVP		0.49
MPC		0.68
ClinPred		0.47	T
GERP RS		2.2
Varity_R		0.12
gMVP		0.45

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: rs773354511; hg19: chr15-64446703;