6-85505762-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX14	NM_153816.6	c.*205C>T		3_prime_UTR_variant	29/29	ENST00000314673.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX14	ENST00000314673.8	c.*205C>T		3_prime_UTR_variant	29/29	1	NM_153816.6	P4

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

Gnomad4 AFR exome AF: 0.0256

Gnomad4 AMR exome AF: 0.00289

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000111

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.00248

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

Gnomad4 AFR AF: 0.0267

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00596 Hom.: 0

Bravo AF: 0.00895

Asia WGS AF: 0.000868 AC: 3 AN: 3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 12, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.1
Dann	Benign	0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs141329378; hg19: chr6-86215480;