NM_014426.4:c.51+5526T>A

Variant names:

• chr20-17962849-A-T
• rs753213
• NM_014426.4:c.51+5526T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014426.4(SNX5):​c.51+5526T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 518,922 control chromosomes in the GnomAD database, including 24,717 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5542 hom., cov: 32)
  • Exomes 𝑓: 0.31 (19175 hom.)
• Consequence: SNX5 NM_014426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.982
• Publications: 13 publications found

Genes affected

SNX5 (HGNC:14969): (sorting nexin 5) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein functions in endosomal sorting, the phosphoinositide-signaling pathway, and macropinocytosis. This gene may play a role in the tumorigenesis of papillary thyroid carcinoma. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

SNORD17 (HGNC:32713): (small nucleolar RNA, C/D box 17)

OVOL2 (HGNC:15804): (ovo like zinc finger 2) This gene encodes a member of the evolutionarily conserved ovo-like protein family. Mammalian members of this family contain a single zinc finger domain composed of a tetrad of C2H2 zinc fingers with variable N- and C-terminal extensions that contain intrinsically disordered domains. Members of this family are involved in epithelial development and differentiation. Knockout of this gene in mouse results in early embryonic lethality with phenotypes that include neurectoderm expansion, impaired vascularization, and heart anomalies. In humans, allelic variants of this gene have been associated with posterior polymorphous corneal dystrophy. [provided by RefSeq, Apr 2016]

OVOL2 Gene-Disease associations (from GenCC):

• posterior polymorphous corneal dystrophy 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• congenital hereditary endothelial dystrophy type I

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• posterior polymorphous corneal dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX5	NM_014426.4	c.51+5526T>A		intron_variant	Intron 1 of 12	ENST00000377759.9	NP_055241.1
SNORD17	NR_003045.1	n.98T>A		non_coding_transcript_exon_variant	Exon 1 of 1
SNX5	NM_152227.3	c.51+5526T>A		intron_variant	Intron 2 of 13		NP_689413.1
SNX5	NM_001282454.2	c.-264-5812T>A		intron_variant	Intron 1 of 12		NP_001269383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX5	ENST00000377759.9	c.51+5526T>A		intron_variant	Intron 1 of 12	1	NM_014426.4	ENSP00000366988.3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38482 AN: 151998 Hom.: 5542 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.243

GnomAD2 exomes AF: 0.307 AC: 71111 AN: 231910 AF XY: 0.315

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.332

Gnomad EAS exome AF: 0.449

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.313 AC: 114952 AN: 366806 Hom.: 19175 Cov.: 0 AF XY: 0.323 AC XY: 67958 AN XY: 210340

African (AFR) AF: 0.126 AC: 1321 AN: 10506

American (AMR) AF: 0.223 AC: 8084 AN: 36298

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 3897 AN: 11744

East Asian (EAS) AF: 0.437 AC: 5761 AN: 13170

South Asian (SAS) AF: 0.416 AC: 27785 AN: 66756

European-Finnish (FIN) AF: 0.340 AC: 5746 AN: 16922

Middle Eastern (MID) AF: 0.215 AC: 603 AN: 2810

European-Non Finnish (NFE) AF: 0.295 AC: 56645 AN: 191970

Other (OTH) AF: 0.307 AC: 5110 AN: 16630

GnomAD4 genome AF: 0.253 AC: 38484 AN: 152116 Hom.: 5542 Cov.: 32 AF XY: 0.261 AC XY: 19384 AN XY: 74370

African (AFR) AF: 0.117 AC: 4874 AN: 41520

American (AMR) AF: 0.253 AC: 3871 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1130 AN: 3466

East Asian (EAS) AF: 0.438 AC: 2259 AN: 5158

South Asian (SAS) AF: 0.432 AC: 2087 AN: 4828

European-Finnish (FIN) AF: 0.344 AC: 3640 AN: 10568

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19750 AN: 67976

Other (OTH) AF: 0.243 AC: 512 AN: 2106

Alfa AF: 0.275 Hom.: 1116

Bravo AF: 0.236

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs753213; hg19: chr20-17943492; COSMIC: COSV66697917; COSMIC: COSV66697917;