16-50677423-G-T

Variant names:

• chr16-50677423-G-T
• rs1131716
• NM_182854.4:c.104C>A

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.104C>A​(p.Pro35Gln) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX20 NM_182854.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• 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=0.07691932).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX20	NM_182854.4	MANE Select	c.104C>A	p.Pro35Gln	missense	Exon 2 of 4	NP_878274.1
	SNX20	NM_153337.3		c.104C>A	p.Pro35Gln	missense	Exon 2 of 4	NP_699168.1
	SNX20	NM_001144972.2		c.104C>A	p.Pro35Gln	missense	Exon 2 of 4	NP_001138444.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX20	ENST00000330943.9	TSL:1 MANE Select	c.104C>A	p.Pro35Gln	missense	Exon 2 of 4	ENSP00000332062.4
	SNX20	ENST00000423026.6	TSL:1	c.104C>A	p.Pro35Gln	missense	Exon 2 of 4	ENSP00000388875.2
	SNX20	ENST00000568993.5	TSL:1	n.104C>A		non_coding_transcript_exon	Exon 2 of 5	ENSP00000454863.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.2
DANN	Benign	0.76
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.035
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.10
Sift	Benign	0.059	T
Sift4G	Benign	0.47	T
Polyphen		0.91	P
Vest4		0.31
MutPred		0.21		Gain of solvent accessibility (P = 0.0055)
MVP		0.14
MPC		1.1
ClinPred		0.18	T
GERP RS		-0.37
Varity_R		0.040
gMVP		0.30
Mutation Taster		=98/2	polymorphism

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: rs1131716; hg19: chr16-50711334; COSMIC: COSV56058527;