rs2310160

Positions:

• chr4-185269140-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378034.2(SNX25):​c.1091+1985C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,842 control chromosomes in the GnomAD database, including 13,831 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 0.42 (13831 hom., cov: 31)
• Consequence: SNX25 NM_001378034.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

Genes affected

SNX25 (HGNC:21883): (sorting nexin 25) Predicted to enable type I transforming growth factor beta receptor binding activity. Involved in negative regulation of pathway-restricted SMAD protein phosphorylation; negative regulation of transforming growth factor beta receptor signaling pathway; and receptor catabolic process. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

SNX25 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX25	NM_001378034.2	c.1091+1985C>T		intron_variant		ENST00000652585.2	NP_001364963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX25	ENST00000652585.2	c.1091+1985C>T		intron_variant			NM_001378034.2	ENSP00000498676.1
SNX25	ENST00000504273.5	c.599+1985C>T		intron_variant		1		ENSP00000426255.1
SNX25	ENST00000264694.13	c.599+1985C>T		intron_variant		5		ENSP00000264694.8
SNX25	ENST00000618785.4	c.-89+1985C>T		intron_variant		5		ENSP00000483653.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64283 AN: 151724 Hom.: 13810 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.424 AC: 64352 AN: 151842 Hom.: 13831 Cov.: 31 AF XY: 0.421 AC XY: 31206 AN XY: 74180

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.420

Alfa AF: 0.432 Hom.: 6824

Bravo AF: 0.423

Asia WGS AF: 0.513 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.58
DANN	Benign	0.81

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: rs2310160; hg19: chr4-186190294;