NM_013321.4:c.95-16446C>T

Variant names:

• chr7-2294751-G-A
• rs10950641
• NM_013321.4:c.95-16446C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_013321.4(SNX8):​c.95-16446C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 152,304 control chromosomes in the GnomAD database, including 92 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 0.029 (92 hom., cov: 32)
• Consequence: SNX8 NM_013321.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• Publications: 5 publications found

Genes affected

SNX8 (HGNC:14972): (sorting nexin 8) Enables identical protein binding activity and phosphatidylinositol binding activity. Involved in early endosome to Golgi transport and intracellular protein transport. Located in early endosome membrane. Colocalizes with retromer complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0293 (4461/152304) while in subpopulation NFE AF = 0.0472 (3214/68030). AF 95% confidence interval is 0.0459. There are 92 homozygotes in GnomAd4. There are 2050 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 92 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX8	NM_013321.4	c.95-16446C>T		intron_variant	Intron 1 of 10	ENST00000222990.8	NP_037453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX8	ENST00000222990.8	c.95-16446C>T		intron_variant	Intron 1 of 10	1	NM_013321.4	ENSP00000222990.3

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4462 AN: 152186 Hom.: 92 Cov.: 32

Gnomad AFR AF: 0.00919

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0292

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

GnomAD4 genome AF: 0.0293 AC: 4461 AN: 152304 Hom.: 92 Cov.: 32 AF XY: 0.0275 AC XY: 2050 AN XY: 74456

African (AFR) AF: 0.00916 AC: 381 AN: 41572

American (AMR) AF: 0.0264 AC: 403 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4822

European-Finnish (FIN) AF: 0.0238 AC: 253 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0472 AC: 3214 AN: 68030

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

Alfa AF: 0.0422 Hom.: 440

Bravo AF: 0.0303

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.53
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism

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: rs10950641; hg19: chr7-2334386;