6-85508320-TAAAAAAAA-TAAAAAAAAAA

Variant names:

• chr6-85508320-T-TAA
• rs765165360
• NM_153816.6:c.2654-263_2654-262dupTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_153816.6(SNX14):​c.2654-263_2654-262dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000772 in 868,110 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00066 (0 hom.)
• Consequence: SNX14 NM_153816.6 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00161 (159/98996) while in subpopulation AFR AF = 0.0057 (155/27194). AF 95% confidence interval is 0.00497. There are 1 homozygotes in GnomAd4. There are 64 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

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.2654-263_2654-262dupTT		intron	N/A	NP_722523.1	Q9Y5W7-1
	SNX14	NM_001350532.2		c.2717-263_2717-262dupTT		intron	N/A	NP_001337461.1	A0A804HKZ1
	SNX14	NM_001350533.2		c.2651-263_2651-262dupTT		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.2654-263_2654-262dupTT		intron	N/A	ENSP00000313121.3	Q9Y5W7-1
	SNX14	ENST00000369627.6	TSL:1	c.2627-263_2627-262dupTT		intron	N/A	ENSP00000358641.2	Q9Y5W7-4
	SNX14	ENST00000346348.7	TSL:1	c.2495-263_2495-262dupTT		intron	N/A	ENSP00000257769.3	Q9Y5W7-2

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 159 AN: 99018 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00571

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000740

GnomAD4 exome AF: 0.000664 AC: 511 AN: 769114 Hom.: 0 Cov.: 0 AF XY: 0.000677 AC XY: 242 AN XY: 357362

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

African (AFR) AF: 0.00397 AC: 57 AN: 14350

American (AMR) AF: 0.000816 AC: 1 AN: 1226

Ashkenazi Jewish (ASJ) AF: 0.000968 AC: 5 AN: 5166

East Asian (EAS) AF: 0.000460 AC: 2 AN: 4346

South Asian (SAS) AF: 0.000656 AC: 10 AN: 15248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 986

Middle Eastern (MID) AF: 0.000638 AC: 1 AN: 1568

European-Non Finnish (NFE) AF: 0.000599 AC: 420 AN: 700680

Other (OTH) AF: 0.000587 AC: 15 AN: 25544

⚠️ 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: 0.00161 AC: 159 AN: 98996 Hom.: 1 Cov.: 31 AF XY: 0.00136 AC XY: 64 AN XY: 46982

African (AFR) AF: 0.00570 AC: 155 AN: 27194

American (AMR) AF: 0.000328 AC: 3 AN: 9148

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

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

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4754

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 46284

Other (OTH) AF: 0.000737 AC: 1 AN: 1356

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs765165360; hg19: chr6-86218038;