6-85508320-TAAAAAAAA-TA

Variant names:

• chr6-85508320-TAAAAAAA-T
• rs765165360
• NM_153816.6:c.2654-268_2654-262delTTTTTTT

Variant summary

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

The NM_153816.6(SNX14):​c.2654-268_2654-262delTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 770,168 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: not found (cov: 31)
  • Exomes 𝑓: 0.000012 (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: Very rare variant in population databases, with high coverage

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.2654-268_2654-262delTTTTTTT		intron	N/A	NP_722523.1	Q9Y5W7-1
	SNX14	NM_001350532.2		c.2717-268_2717-262delTTTTTTT		intron	N/A	NP_001337461.1	A0A804HKZ1
	SNX14	NM_001350533.2		c.2651-268_2651-262delTTTTTTT		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.2654-268_2654-262delTTTTTTT		intron	N/A	ENSP00000313121.3	Q9Y5W7-1
	SNX14	ENST00000369627.6	TSL:1	c.2627-268_2627-262delTTTTTTT		intron	N/A	ENSP00000358641.2	Q9Y5W7-4
	SNX14	ENST00000346348.7	TSL:1	c.2495-268_2495-262delTTTTTTT		intron	N/A	ENSP00000257769.3	Q9Y5W7-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000117 AC: 9 AN: 770168 Hom.: 0 AF XY: 0.00000838 AC XY: 3 AN XY: 357828

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

African (AFR) AF: 0.00 AC: 0 AN: 14396

American (AMR) AF: 0.00 AC: 0 AN: 1228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5170

East Asian (EAS) AF: 0.000230 AC: 1 AN: 4350

South Asian (SAS) AF: 0.00 AC: 0 AN: 15260

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1568

European-Non Finnish (NFE) AF: 0.0000114 AC: 8 AN: 701626

Other (OTH) AF: 0.00 AC: 0 AN: 25584

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000104942), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

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

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;