chr6-85508320-TA-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_153816.6(SNX14):​c.2654-262delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (2 hom., cov: 31)
  • Exomes 𝑓: 0.30 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNX14 NM_153816.6 intron
• Clinical Significance: Likely 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen, PanelApp Australia

ENSG00000271793 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 6-85508320-TA-T is Benign according to our data. Variant chr6-85508320-TA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1206587.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.2654-262delT		intron	N/A	NP_722523.1	Q9Y5W7-1
	SNX14	NM_001350532.2		c.2717-262delT		intron	N/A	NP_001337461.1	A0A804HKZ1
	SNX14	NM_001350533.2		c.2651-262delT		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.2654-262delT		intron	N/A	ENSP00000313121.3	Q9Y5W7-1
	SNX14	ENST00000369627.6	TSL:1	c.2627-262delT		intron	N/A	ENSP00000358641.2	Q9Y5W7-4
	SNX14	ENST00000346348.7	TSL:1	c.2495-262delT		intron	N/A	ENSP00000257769.3	Q9Y5W7-2

Frequencies

GnomAD3 genomes AF: 0.00693 AC: 686 AN: 98994 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.00166

Gnomad EAS AF: 0.00393

Gnomad SAS AF: 0.00275

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.00543

Gnomad NFE AF: 0.00326

Gnomad OTH AF: 0.00740

GnomAD4 exome AF: 0.299 AC: 221523 AN: 740090 Hom.: 4 Cov.: 0 AF XY: 0.299 AC XY: 102884 AN XY: 343578

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

African (AFR) AF: 0.285 AC: 3941 AN: 13838

American (AMR) AF: 0.258 AC: 306 AN: 1186

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1445 AN: 5022

East Asian (EAS) AF: 0.270 AC: 1141 AN: 4224

South Asian (SAS) AF: 0.293 AC: 4272 AN: 14594

European-Finnish (FIN) AF: 0.213 AC: 207 AN: 972

Middle Eastern (MID) AF: 0.312 AC: 471 AN: 1510

European-Non Finnish (NFE) AF: 0.300 AC: 202313 AN: 674164

Other (OTH) AF: 0.302 AC: 7427 AN: 24580

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00695 AC: 688 AN: 98972 Hom.: 2 Cov.: 31 AF XY: 0.00762 AC XY: 358 AN XY: 46978

African (AFR) AF: 0.0126 AC: 344 AN: 27198

American (AMR) AF: 0.00875 AC: 80 AN: 9148

Ashkenazi Jewish (ASJ) AF: 0.00166 AC: 4 AN: 2410

East Asian (EAS) AF: 0.00394 AC: 15 AN: 3804

South Asian (SAS) AF: 0.00246 AC: 8 AN: 3246

European-Finnish (FIN) AF: 0.0158 AC: 75 AN: 4742

Middle Eastern (MID) AF: 0.00595 AC: 1 AN: 168

European-Non Finnish (NFE) AF: 0.00326 AC: 151 AN: 46272

Other (OTH) AF: 0.00737 AC: 10 AN: 1356

Alfa AF: 0.000112 Hom.: 1

ClinVar

ClinVar submissions as Germline

Significance: Likely 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)		0.020		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;