NM_153816.6:c.*205C>T

Variant names:

• chr6-85505762-G-A
• rs141329378
• NM_153816.6:c.*205C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_153816.6(SNX14):​c.*205C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 528,902 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0078 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (5 hom.)
• Consequence: SNX14 NM_153816.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.254
• 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen, PanelApp Australia

ENSG00000271793 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-85505762-G-A is Benign according to our data. Variant chr6-85505762-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1205055.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00777 (1182/152062) while in subpopulation AFR AF = 0.0267 (1108/41474). AF 95% confidence interval is 0.0254. There are 12 homozygotes in GnomAd4. There are 561 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

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.*205C>T		3_prime_UTR	Exon 29 of 29	NP_722523.1	Q9Y5W7-1
	SNX14	NM_001350532.2		c.*205C>T		3_prime_UTR	Exon 30 of 30	NP_001337461.1	A0A804HKZ1
	SNX14	NM_001350533.2		c.*205C>T		3_prime_UTR	Exon 29 of 29	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.*205C>T		3_prime_UTR	Exon 29 of 29	ENSP00000313121.3	Q9Y5W7-1
	SNX14	ENST00000346348.7	TSL:1	c.*205C>T		3_prime_UTR	Exon 26 of 26	ENSP00000257769.3	Q9Y5W7-2
	ENSG00000271793	ENST00000682083.1		n.*2956C>T		non_coding_transcript_exon	Exon 40 of 40	ENSP00000506859.1

Frequencies

GnomAD3 genomes AF: 0.00779 AC: 1183 AN: 151944 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00334

GnomAD4 exome AF: 0.000953 AC: 359 AN: 376840 Hom.: 5 Cov.: 3 AF XY: 0.000765 AC XY: 155 AN XY: 202540

African (AFR) AF: 0.0256 AC: 230 AN: 8968

American (AMR) AF: 0.00289 AC: 34 AN: 11758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12494

East Asian (EAS) AF: 0.00 AC: 0 AN: 24160

South Asian (SAS) AF: 0.000111 AC: 4 AN: 35898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25010

Middle Eastern (MID) AF: 0.00120 AC: 2 AN: 1672

European-Non Finnish (NFE) AF: 0.000149 AC: 35 AN: 235084

Other (OTH) AF: 0.00248 AC: 54 AN: 21796

GnomAD4 genome AF: 0.00777 AC: 1182 AN: 152062 Hom.: 12 Cov.: 32 AF XY: 0.00755 AC XY: 561 AN XY: 74336

African (AFR) AF: 0.0267 AC: 1108 AN: 41474

American (AMR) AF: 0.00366 AC: 56 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10542

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67970

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00684 Hom.: 0

Bravo AF: 0.00895

Asia WGS AF: 0.000868 AC: 3 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.21
PhyloP100		0.25
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: rs141329378; hg19: chr6-86215480;