6-85505665-C-T

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.*302G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00705 in 317,942 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (7 hom.)
• Consequence: SNX14 NM_153816.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.252

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=-0.85).
• BP6: Variant 6-85505665-C-T is Benign according to our data. Variant chr6-85505665-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1194894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00644 (980/152200) while in subpopulation NFE AF= 0.00904 (615/68002). AF 95% confidence interval is 0.00845. There are 3 homozygotes in gnomad4. There are 470 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX14	NM_153816.6	c.*302G>A		3_prime_UTR_variant	29/29	ENST00000314673.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX14	ENST00000314673.8	c.*302G>A		3_prime_UTR_variant	29/29	1	NM_153816.6	P4

Frequencies

GnomAD3 genomes AF: 0.00646 AC: 982 AN: 152082 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00904

Gnomad OTH AF: 0.00815

GnomAD4 exome AF: 0.00762 AC: 1263 AN: 165742 Hom.: 7 Cov.: 0 AF XY: 0.00711 AC XY: 628 AN XY: 88380

Gnomad4 AFR exome AF: 0.00141

Gnomad4 AMR exome AF: 0.00342

Gnomad4 ASJ exome AF: 0.00268

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00379

Gnomad4 FIN exome AF: 0.0161

Gnomad4 NFE exome AF: 0.00884

Gnomad4 OTH exome AF: 0.00651

GnomAD4 genome AF: 0.00644 AC: 980 AN: 152200 Hom.: 3 Cov.: 32 AF XY: 0.00632 AC XY: 470 AN XY: 74412

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.0145

Gnomad4 NFE AF: 0.00904

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00834 Hom.: 3

Bravo AF: 0.00575

Asia WGS AF: 0.000578 AC: 2 AN: 3472

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

Sep 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.0
Dann	Benign	0.60

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: rs41271623; hg19: chr6-86215383;