6-85508320-TAAAAAAAA-TAAAAA

Variant names:

• chr6-85508320-TAAA-T
• rs765165360
• NM_153816.6:c.2654-264_2654-262delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153816.6(SNX14):​c.2654-264_2654-262delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 841,644 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.015 (0 hom.)
• Consequence: SNX14 NM_153816.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Variant has high frequency in the AMR (0.0238) population. However there is too low homozygotes in high coverage region: (expected more than 37, got 0).

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.2654-264_2654-262delTTT		intron	N/A	NP_722523.1	Q9Y5W7-1
	SNX14	NM_001350532.2		c.2717-264_2717-262delTTT		intron	N/A	NP_001337461.1	A0A804HKZ1
	SNX14	NM_001350533.2		c.2651-264_2651-262delTTT		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.2654-264_2654-262delTTT		intron	N/A	ENSP00000313121.3	Q9Y5W7-1
	SNX14	ENST00000369627.6	TSL:1	c.2627-264_2627-262delTTT		intron	N/A	ENSP00000358641.2	Q9Y5W7-4
	SNX14	ENST00000346348.7	TSL:1	c.2495-264_2495-262delTTT		intron	N/A	ENSP00000257769.3	Q9Y5W7-2

Frequencies

GnomAD3 genomes AF: 0.000202 AC: 20 AN: 98980 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000736

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000219

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000422

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000281

Gnomad OTH AF: 0.000741

GnomAD4 exome AF: 0.0151 AC: 11220 AN: 742686 Hom.: 0 AF XY: 0.0151 AC XY: 5202 AN XY: 345108

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

African (AFR) AF: 0.0148 AC: 206 AN: 13936

American (AMR) AF: 0.0283 AC: 33 AN: 1168

Ashkenazi Jewish (ASJ) AF: 0.0178 AC: 89 AN: 4994

East Asian (EAS) AF: 0.0279 AC: 118 AN: 4226

South Asian (SAS) AF: 0.0158 AC: 232 AN: 14724

European-Finnish (FIN) AF: 0.0504 AC: 49 AN: 972

Middle Eastern (MID) AF: 0.0172 AC: 26 AN: 1516

European-Non Finnish (NFE) AF: 0.0149 AC: 10084 AN: 676462

Other (OTH) AF: 0.0155 AC: 383 AN: 24688

⚠️ 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: 0.000202 AC: 20 AN: 98958 Hom.: 0 Cov.: 31 AF XY: 0.000234 AC XY: 11 AN XY: 46964

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

African (AFR) AF: 0.0000735 AC: 2 AN: 27194

American (AMR) AF: 0.000219 AC: 2 AN: 9150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2412

East Asian (EAS) AF: 0.00 AC: 0 AN: 3804

South Asian (SAS) AF: 0.00 AC: 0 AN: 3246

European-Finnish (FIN) AF: 0.000422 AC: 2 AN: 4744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 168

European-Non Finnish (NFE) AF: 0.000281 AC: 13 AN: 46258

Other (OTH) AF: 0.000739 AC: 1 AN: 1354

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000000162093), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8
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;