6-157936048-C-T

Variant names:

• chr6-157936048-C-T
• rs113092501
• NM_016224.5:c.1443+8C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016224.5(SNX9):​c.1443+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,601,802 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (63 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (56 hom.)
• Consequence: SNX9 NM_016224.5 splice_region, intron
• Scores: Splicing: ADA: 0.00005307
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.471
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-157936048-C-T is Benign according to our data. Variant chr6-157936048-C-T is described in ClinVar as Benign. ClinVar VariationId is 774072.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 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.1443+8C>T		splice_region 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.1443+8C>T		splice_region intron	N/A	ENSP00000376024.3	Q9Y5X1
	SNX9	ENST00000971713.1		c.1791+8C>T		splice_region intron	N/A	ENSP00000641772.1
	SNX9	ENST00000681534.1		c.1443+8C>T		splice_region intron	N/A	ENSP00000505127.1	A0A7P0T8C7

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2258 AN: 152212 Hom.: 64 Cov.: 33

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00417 AC: 1012 AN: 242922 AF XY: 0.00320

Gnomad AFR exome AF: 0.0510

Gnomad AMR exome AF: 0.00283

Gnomad ASJ exome AF: 0.00496

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000336

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00181 AC: 2624 AN: 1449470 Hom.: 56 Cov.: 27 AF XY: 0.00164 AC XY: 1180 AN XY: 721038

African (AFR) AF: 0.0541 AC: 1783 AN: 32956

American (AMR) AF: 0.00308 AC: 134 AN: 43440

Ashkenazi Jewish (ASJ) AF: 0.00470 AC: 122 AN: 25944

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.000262 AC: 22 AN: 83834

European-Finnish (FIN) AF: 0.0000750 AC: 4 AN: 53316

Middle Eastern (MID) AF: 0.00505 AC: 29 AN: 5744

European-Non Finnish (NFE) AF: 0.000261 AC: 288 AN: 1104746

Other (OTH) AF: 0.00403 AC: 242 AN: 59982

GnomAD4 genome AF: 0.0149 AC: 2271 AN: 152332 Hom.: 63 Cov.: 33 AF XY: 0.0149 AC XY: 1112 AN XY: 74486

African (AFR) AF: 0.0515 AC: 2139 AN: 41572

American (AMR) AF: 0.00372 AC: 57 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68024

Other (OTH) AF: 0.0137 AC: 29 AN: 2114

Alfa AF: 0.00769 Hom.: 20

Bravo AF: 0.0170

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.72
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000053
dbscSNV1_RF	Benign	0.0
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: rs113092501; hg19: chr6-158357080;