Genetic Variant NM_014426.4:c.51+5526T>A (chr20-17962849-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.982

Variant links:

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]

SNX5 links:

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

SNORD17 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	Exon rank	MANE	Protein	UniProt
SNX5	NM_014426.4 link	c.51+5526T>A	intron_variant	Intron 1 of 12	ENST00000377759.9	NP_055241.1	Q9Y5X3-1
SNX5	NM_152227.3 link	c.51+5526T>A	intron_variant	Intron 2 of 13		NP_689413.1	Q9Y5X3-1
SNX5	NM_001282454.2 link	c.-264-5812T>A	intron_variant	Intron 1 of 12		NP_001269383.1	Q6P5V6
SNORD17	NR_003045.1 link	n.98T>A	non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX5	ENST00000377759.9 link	c.51+5526T>A		intron_variant	Intron 1 of 12	1	NM_014426.4	ENSP00000366988.3		Q9Y5X3-1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38482

AN:

151998

Hom.:

5542

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.307

AC:

71111

AN:

231910

Hom.:

11810

AF XY:

0.315

AC XY:

40361

AN XY:

127936

show subpopulations

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 SAS exome

AF:

0.424

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.:

AF XY:

0.323

AC XY:

67958

AN XY:

210340

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.223

Gnomad4 ASJ exome

AF:

0.332

Gnomad4 EAS exome

AF:

0.437

Gnomad4 SAS exome

AF:

0.416

Gnomad4 FIN exome

AF:

0.340

Gnomad4 NFE exome

AF:

0.295

Gnomad4 OTH exome

AF:

0.307

GnomAD4 genome

AF:

0.253

AC:

38484

AN:

152116

Hom.:

5542

Cov.:

AF XY:

0.261

AC XY:

19384

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.253

Gnomad4 ASJ

AF:

0.326

Gnomad4 EAS

AF:

0.438

Gnomad4 SAS

AF:

0.432

Gnomad4 FIN

AF:

0.344

Gnomad4 NFE

AF:

0.291

Gnomad4 OTH

AF:

0.243

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

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over