Genetic Variant SNX14:c.2654-266_2654-262delTTTTT (chr6-85508320-TAAAAA-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_153816.6(SNX14):c.2654-266_2654-262delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00055 in 868,008 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 0.00027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00059 ( 0 hom. )

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: Likely_benign. The variant received -4 ACMG points.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000273 (27/99008) while in subpopulation AMR AF = 0.000437 (4/9152). AF 95% confidence interval is 0.000286. There are 0 homozygotes in GnomAd4. There are 19 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNX14	NM_153816.6	MANE Select	c.2654-266_2654-262delTTTTT	intron	N/A	NP_722523.1	Q9Y5W7-1
SNX14	NM_001350532.2		c.2717-266_2717-262delTTTTT	intron	N/A	NP_001337461.1	A0A804HKZ1
SNX14	NM_001350533.2		c.2651-266_2651-262delTTTTT	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.2654-266_2654-262delTTTTT	intron	N/A	ENSP00000313121.3	Q9Y5W7-1
SNX14	ENST00000369627.6	TSL:1	c.2627-266_2627-262delTTTTT	intron	N/A	ENSP00000358641.2	Q9Y5W7-4
SNX14	ENST00000346348.7	TSL:1	c.2495-266_2495-262delTTTTT	intron	N/A	ENSP00000257769.3	Q9Y5W7-2

Frequencies

GnomAD3 genomes

AF:

0.000273

AC:

AN:

99030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000437

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:

0.000432

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000585

AC:

450

AN:

769000

Hom.:

AF XY:

0.000557

AC XY:

199

AN XY:

357286

show subpopulations

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

African (AFR)

AF:

0.000209

AC:

AN:

14368

American (AMR)

AF:

0.000817

AC:

AN:

1224

Ashkenazi Jewish (ASJ)

AF:

0.000387

AC:

AN:

5164

East Asian (EAS)

AF:

0.000922

AC:

AN:

4338

South Asian (SAS)

AF:

0.000787

AC:

AN:

15240

European-Finnish (FIN)

AF:

0.00304

AC:

AN:

986

Middle Eastern (MID)

AF:

0.000640

AC:

AN:

1562

European-Non Finnish (NFE)

AF:

0.000592

AC:

415

AN:

700576

Other (OTH)

AF:

0.000352

AC:

AN:

25542

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.293

Heterozygous variant carriers

128

170

213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000273

AC:

AN:

99008

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

46990

show subpopulations

African (AFR)

AF:

0.000110

AC:

AN:

27200

American (AMR)

AF:

0.000437

AC:

AN:

9152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2414

East Asian (EAS)

AF:

0.00

AC:

AN:

3804

South Asian (SAS)

AF:

0.00

AC:

AN:

3246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4754

Middle Eastern (MID)

AF:

0.00

AC:

AN:

168

European-Non Finnish (NFE)

AF:

0.000432

AC:

AN:

46286

Other (OTH)

AF:

0.00

AC:

AN:

1356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

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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6-85508320-TAAAAAAAA-TAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over