8-81839802-T-G

Position:

• chr8-81839802-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152836.3(SNX16):​c.185A>C​(p.Asp62Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 152,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: SNX16 NM_152836.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

Genes affected

SNX16 (HGNC:14980): (sorting nexin 16) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. The protein encoded by this gene associates with late endosome membranes as is involved in tubule formation, cholesterol transport, and transport of tetraspanin CD81. The encoded protein also inhibits cell migration and tumorigenesis. [provided by RefSeq, Jan 2017]

SNX16 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09930363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX16	NM_152836.3	c.185A>C	p.Asp62Ala	missense_variant	2/8	ENST00000345957.9	NP_690049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX16	ENST00000345957.9	c.185A>C	p.Asp62Ala	missense_variant	2/8	1	NM_152836.3	ENSP00000322652.4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.00000756

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

Oct 27, 2023

The c.185A>C (p.D62A) alteration is located in exon 3 (coding exon 1) of the SNX16 gene. This alteration results from a A to C substitution at nucleotide position 185, causing the aspartic acid (D) at amino acid position 62 to be replaced by an alanine (A). 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	0.090
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	.;T;T;T;.;T;.;.
Eigen	Benign	-0.087
Eigen_PC	Benign	0.025
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.81	T;T;T;.;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.099	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.;L;.;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.45	N;N;.;N;D;N;D;D
REVEL	Benign	0.080
Sift	Uncertain	0.0080	D;D;.;D;D;D;D;D
Sift4G	Uncertain	0.045	D;T;T;T;.;.;.;.
Polyphen		0.48	.;P;.;P;.;.;.;.
Vest4		0.10
MutPred		0.13		Loss of phosphorylation at T64 (P = 0.156);Loss of phosphorylation at T64 (P = 0.156);Loss of phosphorylation at T64 (P = 0.156);Loss of phosphorylation at T64 (P = 0.156);Loss of phosphorylation at T64 (P = 0.156);Loss of phosphorylation at T64 (P = 0.156);Loss of phosphorylation at T64 (P = 0.156);Loss of phosphorylation at T64 (P = 0.156);
MVP		0.59
MPC		0.36
ClinPred		0.60	D
GERP RS		5.6
Varity_R		0.088
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1811655128; hg19: chr8-82752037;