6-157868514-G-C

Variant names:

• chr6-157868514-G-C
• rs6937267
• NM_016224.5:c.99+881G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016224.5(SNX9):​c.99+881G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 152,206 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.032 (211 hom., cov: 32)
• Consequence: SNX9 NM_016224.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• Publications: 1 publications found

Genes affected

SNX9 (HGNC:14973): (sorting nexin 9) This gene encodes a member of the sorting nexin family. Members of this family contain a phosphoinositide binding domain, and are involved in intracellular trafficking. The encoded protein does not contain a coiled coil region, like some family members, but does contain a SRC homology domain near its N-terminus. The encoded protein is reported to have a variety of interaction partners, including of adaptor protein 2 , dynamin, tyrosine kinase non-receptor 2, Wiskott-Aldrich syndrome-like, and ARP3 actin-related protein 3. The encoded protein is implicated in several stages of intracellular trafficking, including endocytosis, macropinocytosis, and F-actin nucleation. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016224.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX9	NM_016224.5	MANE Select	c.99+881G>C		intron	N/A	NP_057308.1	Q9Y5X1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX9	ENST00000392185.8	TSL:1 MANE Select	c.99+881G>C		intron	N/A	ENSP00000376024.3	Q9Y5X1
	SNX9	ENST00000971713.1		c.99+881G>C		intron	N/A	ENSP00000641772.1
	SNX9	ENST00000681534.1		c.99+881G>C		intron	N/A	ENSP00000505127.1	A0A7P0T8C7

Frequencies

GnomAD3 genomes AF: 0.0324 AC: 4926 AN: 152088 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00863

Gnomad OTH AF: 0.0239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0324 AC: 4932 AN: 152206 Hom.: 211 Cov.: 32 AF XY: 0.0311 AC XY: 2317 AN XY: 74432

African (AFR) AF: 0.0936 AC: 3883 AN: 41496

American (AMR) AF: 0.0169 AC: 259 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4820

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00862 AC: 586 AN: 68008

Other (OTH) AF: 0.0237 AC: 50 AN: 2112

Alfa AF: 0.0218 Hom.: 15

Bravo AF: 0.0361

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.63
PhyloP100		0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
Mutation Taster		=100/0	polymorphism (auto)

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: rs6937267; hg19: chr6-158289546;