chr16-50673591-G-A

Position:

• chr16-50673591-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_182854.4(SNX20):​c.766C>T​(p.Arg256Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000696 in 1,436,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: SNX20 NM_182854.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057897836).
• BP6: Variant 16-50673591-G-A is Benign according to our data. Variant chr16-50673591-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3321293.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX20	NM_182854.4	c.766C>T	p.Arg256Cys	missense_variant	4/4	ENST00000330943.9
SNX20	NM_001144972.2	c.282+2179C>T		intron_variant
SNX20	NM_153337.3	c.282+2179C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX20	ENST00000330943.9	c.766C>T	p.Arg256Cys	missense_variant	4/4	1	NM_182854.4	P1
SNX20	ENST00000423026.6	c.282+2179C>T		intron_variant		1
SNX20	ENST00000568993.5	c.282+2179C>T		intron_variant, NMD_transcript_variant		1
SNX20	ENST00000300590.7	c.282+2179C>T		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000185 AC: 4 AN: 216040 Hom.: 0 AF XY: 0.0000166 AC XY: 2 AN XY: 120546

Gnomad AFR exome AF: 0.0000879

Gnomad AMR exome AF: 0.0000952

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000696 AC: 10 AN: 1436732 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2 AN XY: 714686

Gnomad4 AFR exome AF: 0.0000319

Gnomad4 AMR exome AF: 0.0000704

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000543

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.97	N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.14
Sift	Benign	0.23	T
Sift4G	Benign	0.19	T
Polyphen		0.0020	B
Vest4		0.070
MutPred		0.37		Loss of MoRF binding (P = 0.006);
MVP		0.25
MPC		0.67
ClinPred		0.043	T
GERP RS		-2.7
Varity_R		0.055
gMVP		0.14

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: rs1415609887; hg19: chr16-50707502;