dbSNP rs765165360: SNX14:c.2654-269_2654-262delTTTTTTTT (chr6-85508320-TAAAAAAAA-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_153816.6(SNX14):c.2654-269_2654-262delTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 99,030 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 0.000010 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SNX14
NM_153816.6 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.80

Publications

0 publications found

Variant links:

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

SNX14 links:

ENSG00000271793 (HGNC:):

ENSG00000271793 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNX14	NM_153816.6	MANE Select	c.2654-269_2654-262delTTTTTTTT	intron	N/A	NP_722523.1	Q9Y5W7-1
SNX14	NM_001350532.2		c.2717-269_2717-262delTTTTTTTT	intron	N/A	NP_001337461.1	A0A804HKZ1
SNX14	NM_001350533.2		c.2651-269_2651-262delTTTTTTTT	intron	N/A	NP_001337462.1	A0A804HKC6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNX14	ENST00000314673.8	TSL:1 MANE Select	c.2654-269_2654-262delTTTTTTTT	intron	N/A	ENSP00000313121.3	Q9Y5W7-1
SNX14	ENST00000369627.6	TSL:1	c.2627-269_2627-262delTTTTTTTT	intron	N/A	ENSP00000358641.2	Q9Y5W7-4
SNX14	ENST00000346348.7	TSL:1	c.2495-269_2495-262delTTTTTTTT	intron	N/A	ENSP00000257769.3	Q9Y5W7-2

Frequencies

GnomAD3 genomes

AF:

0.0000101

AC:

AN:

99030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000216

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

770178

Hom.:

AF XY:

0.00

AC XY:

AN XY:

357834

African (AFR)

AF:

0.00

AC:

AN:

14396

American (AMR)

AF:

0.00

AC:

AN:

1228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5170

East Asian (EAS)

AF:

0.00

AC:

AN:

4350

South Asian (SAS)

AF:

0.00

AC:

AN:

15260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1568

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

701636

Other (OTH)

AF:

0.00

AC:

AN:

25584

GnomAD4 genome

AF:

0.0000101

AC:

AN:

99030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

46988

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

27162

American (AMR)

AF:

0.00

AC:

AN:

9144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2414

East Asian (EAS)

AF:

0.00

AC:

AN:

3818

South Asian (SAS)

AF:

0.00

AC:

AN:

3274

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4754

Middle Eastern (MID)

AF:

0.00

AC:

AN:

184

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

46300

Other (OTH)

AF:

0.00

AC:

AN:

1352

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over