6-85508320-TAAAAAAAA-TAAAAAAAAA

Variant names:

• chr6-85508320-T-TA
• rs765165360
• NM_153816.6:c.2654-262dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_153816.6(SNX14):​c.2654-262dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 866,734 control chromosomes in the GnomAD database, including 128 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (128 hom., cov: 31)
  • Exomes 𝑓: 0.019 (0 hom.)
• Consequence: SNX14 NM_153816.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.381
• Publications: 0 publications found

Genes affected

SNX14 (HGNC:14977): (sorting nexin 14) This gene encodes a member of the sorting nexin family. Members of this family have a phox (PX) phosphoinositide binding domain and are involved in intracellular trafficking. The encoded protein also contains a regulator of G protein signaling (RGS) domain. Regulator of G protein signaling family members are regulatory molecules that act as GTPase activating proteins for G alpha subunits of heterotrimeric G proteins. Alternate splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

SNX14 Gene-Disease associations (from GenCC):

• autosomal recessive spinocerebellar ataxia 20

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P, Ambry Genetics, PanelApp Australia

ENSG00000271793 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-85508320-T-TA is Benign according to our data. Variant chr6-85508320-T-TA is described in ClinVar as Benign. ClinVar VariationId is 1246206.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153816.6. 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
	SNX14	NM_153816.6	MANE Select	c.2654-262dupT		intron	N/A	NP_722523.1	Q9Y5W7-1
	SNX14	NM_001350532.2		c.2717-262dupT		intron	N/A	NP_001337461.1	A0A804HKZ1
	SNX14	NM_001350533.2		c.2651-262dupT		intron	N/A	NP_001337462.1	A0A804HKC6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX14	ENST00000314673.8	TSL:1 MANE Select	c.2654-262dupT		intron	N/A	ENSP00000313121.3	Q9Y5W7-1
	SNX14	ENST00000369627.6	TSL:1	c.2627-262dupT		intron	N/A	ENSP00000358641.2	Q9Y5W7-4
	SNX14	ENST00000346348.7	TSL:1	c.2495-262dupT		intron	N/A	ENSP00000257769.3	Q9Y5W7-2

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 3331 AN: 98990 Hom.: 128 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.00159

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.00458

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.0109

Gnomad NFE AF: 0.00335

Gnomad OTH AF: 0.0214

GnomAD4 exome AF: 0.0189 AC: 14548 AN: 767766 Hom.: 0 Cov.: 0 AF XY: 0.0185 AC XY: 6601 AN XY: 356654

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0533 AC: 762 AN: 14298

American (AMR) AF: 0.0172 AC: 21 AN: 1224

Ashkenazi Jewish (ASJ) AF: 0.0142 AC: 73 AN: 5158

East Asian (EAS) AF: 0.0166 AC: 72 AN: 4346

South Asian (SAS) AF: 0.0184 AC: 280 AN: 15214

European-Finnish (FIN) AF: 0.0183 AC: 18 AN: 984

Middle Eastern (MID) AF: 0.0230 AC: 36 AN: 1568

European-Non Finnish (NFE) AF: 0.0183 AC: 12793 AN: 699476

Other (OTH) AF: 0.0193 AC: 493 AN: 25498

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0337 AC: 3331 AN: 98968 Hom.: 128 Cov.: 31 AF XY: 0.0328 AC XY: 1542 AN XY: 46974

African (AFR) AF: 0.108 AC: 2928 AN: 27184

American (AMR) AF: 0.0151 AC: 138 AN: 9146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2414

East Asian (EAS) AF: 0.0142 AC: 54 AN: 3804

South Asian (SAS) AF: 0.00462 AC: 15 AN: 3246

European-Finnish (FIN) AF: 0.00189 AC: 9 AN: 4756

Middle Eastern (MID) AF: 0.0119 AC: 2 AN: 168

European-Non Finnish (NFE) AF: 0.00335 AC: 155 AN: 46266

Other (OTH) AF: 0.0214 AC: 29 AN: 1356

Alfa AF: 0.00124 Hom.: 1

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
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

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: rs765165360; hg19: chr6-86218038;