1-151683361-C-T

Variant names:

• chr1-151683361-C-T
• rs115166911
• NM_001330723.2:c.1155C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001330723.2(SNX27):​c.1155C>T​(p.Val385Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,611,368 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (18 hom., cov: 31)
  • Exomes 𝑓: 0.00059 (6 hom.)
• Consequence: SNX27 NM_001330723.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.07
• Publications: 0 publications found

Genes affected

SNX27 (HGNC:20073): (sorting nexin 27) This gene encodes a member of the sorting nexin family, a diverse group of cytoplasmic and membrane-associated proteins involved in endocytosis of plasma membrane receptors and protein trafficking through these compartments. All members of this protein family contain a phosphoinositide binding domain (PX domain). A highly similar protein in mouse is responsible for the specific recruitment of an isoform of serotonin 5-hydroxytryptamine 4 receptor into early endosomes, suggesting the analogous role for the human protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-151683361-C-T is Benign according to our data. Variant chr1-151683361-C-T is described in ClinVar as Benign. ClinVar VariationId is 462803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00637 (969/152214) while in subpopulation AFR AF = 0.022 (912/41514). AF 95% confidence interval is 0.0208. There are 18 homozygotes in GnomAd4. There are 455 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 969 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330723.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX27	NM_001330723.2	MANE Select	c.1155C>T	p.Val385Val	synonymous	Exon 8 of 12	NP_001317652.1
	SNX27	NM_030918.6		c.1155C>T	p.Val385Val	synonymous	Exon 8 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.852C>T	p.Val284Val	synonymous	Exon 7 of 11	NP_001424530.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX27	ENST00000458013.7	TSL:5 MANE Select	c.1155C>T	p.Val385Val	synonymous	Exon 8 of 12	ENSP00000400333.2
	SNX27	ENST00000368843.8	TSL:1	c.1155C>T	p.Val385Val	synonymous	Exon 8 of 12	ENSP00000357836.3
	SNX27	ENST00000368838.2	TSL:1	c.750C>T	p.Val250Val	synonymous	Exon 7 of 10	ENSP00000357831.2

Frequencies

GnomAD3 genomes AF: 0.00638 AC: 970 AN: 152096 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00149 AC: 371 AN: 249074 AF XY: 0.00113

Gnomad AFR exome AF: 0.0213

Gnomad AMR exome AF: 0.000414

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000659

GnomAD4 exome AF: 0.000593 AC: 866 AN: 1459154 Hom.: 6 Cov.: 30 AF XY: 0.000504 AC XY: 366 AN XY: 725904

African (AFR) AF: 0.0227 AC: 755 AN: 33246

American (AMR) AF: 0.000476 AC: 21 AN: 44148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.000117 AC: 10 AN: 85804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5728

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1110940

Other (OTH) AF: 0.00103 AC: 62 AN: 60266

GnomAD4 genome AF: 0.00637 AC: 969 AN: 152214 Hom.: 18 Cov.: 31 AF XY: 0.00611 AC XY: 455 AN XY: 74418

African (AFR) AF: 0.0220 AC: 912 AN: 41514

American (AMR) AF: 0.00281 AC: 43 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

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

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68018

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00277 Hom.: 2

Bravo AF: 0.00726

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Severe myoclonic epilepsy in infancy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.0
DANN	Benign	0.57
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs115166911; hg19: chr1-151655837;