16-50675795-T-G

Variant names:

• chr16-50675795-T-G
• rs763492085
• NM_182854.4:c.257A>C

Variant summary

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

The NM_182854.4(SNX20):​c.257A>C​(p.Glu86Ala) 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. E86G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX20 NM_182854.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• Publications: 0 publications found

Genes affected

SNX20 (HGNC:30390): (sorting nexin 20) SNX20 interacts with the cytoplasmic domain of PSGL1 (SELPLG; MIM 600738) and cycles PSGL1 into endosomes.[supplied by OMIM, Feb 2010]

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=0.1286434).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182854.4. 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
	SNX20	NM_182854.4	MANE Select	c.257A>C	p.Glu86Ala	missense	Exon 3 of 4	NP_878274.1	Q7Z614-1
	SNX20	NM_153337.3		c.257A>C	p.Glu86Ala	missense	Exon 3 of 4	NP_699168.1	Q7Z614-3
	SNX20	NM_001144972.2		c.257A>C	p.Glu86Ala	missense	Exon 3 of 4	NP_001138444.1	Q7Z614-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX20	ENST00000330943.9	TSL:1 MANE Select	c.257A>C	p.Glu86Ala	missense	Exon 3 of 4	ENSP00000332062.4	Q7Z614-1
	SNX20	ENST00000423026.6	TSL:1	c.257A>C	p.Glu86Ala	missense	Exon 3 of 4	ENSP00000388875.2	Q7Z614-4
	SNX20	ENST00000568993.5	TSL:1	n.257A>C		non_coding_transcript_exon	Exon 3 of 5	ENSP00000454863.1	Q7Z614-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.028
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Benign	0.22	T
Sift4G	Benign	0.39	T
Polyphen		0.61	P
Vest4		0.14
MutPred		0.51		Gain of MoRF binding (P = 0.0169)
MVP		0.40
MPC		0.56
ClinPred		0.67	D
GERP RS		4.6
Varity_R		0.093
gMVP		0.44

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: rs763492085; hg19: chr16-50709706;