rs78681505

Variant names:

• chr6-85507372-T-C
• rs78681505
• NM_153816.6:c.2746-83A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153816.6(SNX14):​c.2746-83A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,188,996 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (176 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (94 hom.)
• Consequence: SNX14 NM_153816.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.409
• 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=-0.92).
• BP6: Variant 6-85507372-T-C is Benign according to our data. Variant chr6-85507372-T-C is described in ClinVar as Benign. ClinVar VariationId is 1226900.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.082 is higher than 0.05.

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.2746-83A>G		intron	N/A	NP_722523.1	Q9Y5W7-1
	SNX14	NM_001350532.2		c.2809-83A>G		intron	N/A	NP_001337461.1	A0A804HKZ1
	SNX14	NM_001350533.2		c.2743-83A>G		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.2746-83A>G		intron	N/A	ENSP00000313121.3	Q9Y5W7-1
	SNX14	ENST00000369627.6	TSL:1	c.2719-83A>G		intron	N/A	ENSP00000358641.2	Q9Y5W7-4
	SNX14	ENST00000346348.7	TSL:1	c.2587-83A>G		intron	N/A	ENSP00000257769.3	Q9Y5W7-2

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3648 AN: 152076 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00838

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.00233 AC: 2418 AN: 1036802 Hom.: 94 AF XY: 0.00206 AC XY: 1087 AN XY: 527084

African (AFR) AF: 0.0829 AC: 1939 AN: 23402

American (AMR) AF: 0.00410 AC: 127 AN: 30978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21400

East Asian (EAS) AF: 0.0000274 AC: 1 AN: 36514

South Asian (SAS) AF: 0.000118 AC: 8 AN: 67660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50150

Middle Eastern (MID) AF: 0.00373 AC: 16 AN: 4286

European-Non Finnish (NFE) AF: 0.000108 AC: 82 AN: 756876

Other (OTH) AF: 0.00538 AC: 245 AN: 45536

GnomAD4 genome AF: 0.0241 AC: 3670 AN: 152194 Hom.: 176 Cov.: 32 AF XY: 0.0231 AC XY: 1721 AN XY: 74418

African (AFR) AF: 0.0843 AC: 3499 AN: 41514

American (AMR) AF: 0.00837 AC: 128 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68000

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.0205 Hom.: 13

Bravo AF: 0.0273

Asia WGS AF: 0.00549 AC: 20 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.92
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs78681505; hg19: chr6-86217090;