NM_153816.6:c.2745+19C>G

Variant names:

• chr6-85507949-G-C
• rs201483566
• NM_153816.6:c.2745+19C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_153816.6(SNX14):​c.2745+19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000586 in 1,604,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: SNX14 NM_153816.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 6-85507949-G-C is Benign according to our data. Variant chr6-85507949-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1990293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000355 (54/152188) while in subpopulation AFR AF = 0.00125 (52/41506). AF 95% confidence interval is 0.000981. There are 0 homozygotes in GnomAd4. There are 24 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX14	NM_153816.6	MANE Select	c.2745+19C>G		intron	N/A	NP_722523.1	Q9Y5W7-1
	SNX14	NM_001350532.2		c.2808+19C>G		intron	N/A	NP_001337461.1	A0A804HKZ1
	SNX14	NM_001350533.2		c.2742+19C>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.2745+19C>G		intron	N/A	ENSP00000313121.3	Q9Y5W7-1
	SNX14	ENST00000369627.6	TSL:1	c.2718+19C>G		intron	N/A	ENSP00000358641.2	Q9Y5W7-4
	SNX14	ENST00000346348.7	TSL:1	c.2586+19C>G		intron	N/A	ENSP00000257769.3	Q9Y5W7-2

Frequencies

GnomAD3 genomes AF: 0.000355 AC: 54 AN: 152070 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000645 AC: 16 AN: 248202 AF XY: 0.0000521

Gnomad AFR exome AF: 0.000933

Gnomad AMR exome AF: 0.0000297

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000275 AC: 40 AN: 1452622 Hom.: 0 Cov.: 27 AF XY: 0.0000221 AC XY: 16 AN XY: 722970

African (AFR) AF: 0.00106 AC: 35 AN: 33162

American (AMR) AF: 0.0000452 AC: 2 AN: 44260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.00 AC: 0 AN: 85500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105380

Other (OTH) AF: 0.0000500 AC: 3 AN: 60002

GnomAD4 genome AF: 0.000355 AC: 54 AN: 152188 Hom.: 0 Cov.: 31 AF XY: 0.000323 AC XY: 24 AN XY: 74418

African (AFR) AF: 0.00125 AC: 52 AN: 41506

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000416

ClinVar

ClinVar submissions

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	-0.96
CADD	Benign	0.24
DANN	Benign	0.34
PhyloP100		-1.7

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: rs201483566; hg19: chr6-86217667;