chr16-50677457-G-C

Position:

• chr16-50677457-G-C

Variant summary

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

The NM_182854.4(SNX20):​c.70C>G​(p.Gln24Glu) 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: -0.667

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=0.040540725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX20	NM_182854.4	c.70C>G	p.Gln24Glu	missense_variant	2/4	ENST00000330943.9
SNX20	NM_153337.3	c.70C>G	p.Gln24Glu	missense_variant	2/4
SNX20	NM_001144972.2	c.70C>G	p.Gln24Glu	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX20	ENST00000330943.9	c.70C>G	p.Gln24Glu	missense_variant	2/4	1	NM_182854.4	P1
SNX20	ENST00000423026.6	c.70C>G	p.Gln24Glu	missense_variant	2/4	1
SNX20	ENST00000568993.5	c.70C>G	p.Gln24Glu	missense_variant, NMD_transcript_variant	2/5	1
SNX20	ENST00000300590.7	c.70C>G	p.Gln24Glu	missense_variant	2/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000227

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

Apr 08, 2024

The c.70C>G (p.Q24E) alteration is located in exon 2 (coding exon 1) of the SNX20 gene. This alteration results from a C to G substitution at nucleotide position 70, causing the glutamine (Q) at amino acid position 24 to be replaced by a glutamic acid (E). 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	0.071
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.016
DANN	Benign	0.61
DEOGEN2	Benign	0.0024	.;.;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.54	T;.;T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.041	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.090	N;N;N;.
REVEL	Benign	0.011
Sift	Benign	0.28	T;T;T;.
Sift4G	Benign	0.59	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.041
MVP		0.067
MPC		0.53
ClinPred		0.065	T
GERP RS		-3.9
Varity_R		0.035
gMVP		0.13

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: rs1261221008; hg19: chr16-50711368;