NM_001330723.2:c.984T>C

Variant names:

• chr1-151666010-T-C
• rs150091333
• NM_001330723.2:c.984T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001330723.2(SNX27):​c.984T>C​(p.Phe328Phe) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000834 in 1,609,738 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (6 hom.)
• Consequence: SNX27 NM_001330723.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.001161
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.37
• Publications: 2 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]

SNX27 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 1-151666010-T-C is Benign according to our data. Variant chr1-151666010-T-C is described in ClinVar as Benign. ClinVar VariationId is 462822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.37 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00412 (628/152370) while in subpopulation AFR AF = 0.0134 (559/41592). AF 95% confidence interval is 0.0125. There are 2 homozygotes in GnomAd4. There are 283 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR 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.984T>C	p.Phe328Phe	splice_region synonymous	Exon 6 of 12	NP_001317652.1	Q96L92-1
	SNX27	NM_030918.6		c.984T>C	p.Phe328Phe	splice_region synonymous	Exon 6 of 12	NP_112180.4
	SNX27	NM_001437601.1		c.681T>C	p.Phe227Phe	splice_region synonymous	Exon 5 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.984T>C	p.Phe328Phe	splice_region synonymous	Exon 6 of 12	ENSP00000400333.2	Q96L92-1
	SNX27	ENST00000368843.8	TSL:1	c.984T>C	p.Phe328Phe	splice_region synonymous	Exon 6 of 12	ENSP00000357836.3	Q96L92-3
	SNX27	ENST00000368838.2	TSL:1	c.579T>C	p.Phe193Phe	splice_region synonymous	Exon 5 of 10	ENSP00000357831.2	A0A5H1ZRP6

Frequencies

GnomAD3 genomes AF: 0.00411 AC: 626 AN: 152252 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00119 AC: 298 AN: 249520 AF XY: 0.000867

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.000444

Gnomad ASJ exome AF: 0.00536

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000706

Gnomad OTH exome AF: 0.000990

GnomAD4 exome AF: 0.000490 AC: 714 AN: 1457368 Hom.: 6 Cov.: 29 AF XY: 0.000466 AC XY: 338 AN XY: 725004

African (AFR) AF: 0.0131 AC: 439 AN: 33390

American (AMR) AF: 0.000360 AC: 16 AN: 44470

Ashkenazi Jewish (ASJ) AF: 0.00579 AC: 151 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5756

European-Non Finnish (NFE) AF: 0.0000361 AC: 40 AN: 1108848

Other (OTH) AF: 0.00106 AC: 64 AN: 60176

GnomAD4 genome AF: 0.00412 AC: 628 AN: 152370 Hom.: 2 Cov.: 32 AF XY: 0.00380 AC XY: 283 AN XY: 74510

African (AFR) AF: 0.0134 AC: 559 AN: 41592

American (AMR) AF: 0.00118 AC: 18 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68040

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00173 Hom.: 1

Bravo AF: 0.00420

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Severe myoclonic epilepsy in infancy (1)
-	-	1	SNX27-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		1.4
Mutation Taster		=40/60	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.020
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: rs150091333; hg19: chr1-151638486;