chr16-50677468-G-T

Position:

• chr16-50677468-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182854.4(SNX20):​c.59C>A​(p.Thr20Lys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX20 NM_182854.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.806

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0636158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX20	NM_182854.4	c.59C>A	p.Thr20Lys	missense_variant	2/4	ENST00000330943.9
SNX20	NM_153337.3	c.59C>A	p.Thr20Lys	missense_variant	2/4
SNX20	NM_001144972.2	c.59C>A	p.Thr20Lys	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX20	ENST00000330943.9	c.59C>A	p.Thr20Lys	missense_variant	2/4	1	NM_182854.4	P1
SNX20	ENST00000423026.6	c.59C>A	p.Thr20Lys	missense_variant	2/4	1
SNX20	ENST00000568993.5	c.59C>A	p.Thr20Lys	missense_variant, NMD_transcript_variant	2/5	1
SNX20	ENST00000300590.7	c.59C>A	p.Thr20Lys	missense_variant	2/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Feb 10, 2023

The c.59C>A (p.T20K) alteration is located in exon 2 (coding exon 1) of the SNX20 gene. This alteration results from a C to A substitution at nucleotide position 59, causing the threonine (T) at amino acid position 20 to be replaced by a lysine (K). 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	0.091
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.31
DANN	Benign	0.65
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.65	T;.;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.064	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.9	N;N;N;.
REVEL	Benign	0.0020
Sift	Benign	0.062	T;D;T;.
Sift4G	Benign	0.24	T;T;T;T
Polyphen		0.28	B;B;B;.
Vest4		0.12
MutPred		0.27		Gain of methylation at T20 (P = 0.0039);Gain of methylation at T20 (P = 0.0039);Gain of methylation at T20 (P = 0.0039);Gain of methylation at T20 (P = 0.0039);
MVP		0.12
MPC		0.63
ClinPred		0.15	T
GERP RS		-3.6
Varity_R		0.049
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-50711379;