rs1181173678

Variant names:

• chr1-151612257-G-A
• rs1181173678
• NM_001330723.2:c.56G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001437602.1(SNX27):​c.-183G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000464 in 1,294,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: SNX27 NM_001437602.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.34
• 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]

ENSG00000250734 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28970522).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001437602.1. 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.56G>A	p.Gly19Asp	missense	Exon 1 of 12	NP_001317652.1	Q96L92-1
	SNX27	NM_001437602.1		c.-183G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001424531.1
	SNX27	NM_001437604.1		c.-183G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001424533.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX27	ENST00000458013.7	TSL:5 MANE Select	c.56G>A	p.Gly19Asp	missense	Exon 1 of 12	ENSP00000400333.2	Q96L92-1
	SNX27	ENST00000368843.8	TSL:1	c.56G>A	p.Gly19Asp	missense	Exon 1 of 12	ENSP00000357836.3	Q96L92-3
	SNX27	ENST00000368841.7	TSL:1	n.56G>A		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2	H7C603

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 53104 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000464 AC: 6 AN: 1294160 Hom.: 0 Cov.: 31 AF XY: 0.00000158 AC XY: 1 AN XY: 634870

African (AFR) AF: 0.00 AC: 0 AN: 26164

American (AMR) AF: 0.00 AC: 0 AN: 17930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19874

East Asian (EAS) AF: 0.00 AC: 0 AN: 28844

South Asian (SAS) AF: 0.00 AC: 0 AN: 65528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5190

European-Non Finnish (NFE) AF: 0.00000580 AC: 6 AN: 1034550

Other (OTH) AF: 0.00 AC: 0 AN: 53356

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	1	-	Severe myoclonic epilepsy in infancy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T
Eigen	Benign	0.038
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.58	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.3
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.10
Sift	Benign	0.15	T
Sift4G	Benign	0.45	T
Polyphen		0.91	P
Vest4		0.27
MutPred		0.32		Loss of methylation at R16 (P = 0.0492)
MVP		0.21
MPC		0.80
ClinPred		0.50	D
GERP RS		3.9
PromoterAI		0.30	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.27
Mutation Taster		=87/13	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: rs1181173678; hg19: chr1-151584733;