1-151612258-T-TGGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001330723.2(SNX27):c.69_71dup(p.Gly24dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,440,430 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (14 hom.)
• Consequence: SNX27 NM_001330723.2 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.07

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-151612258-T-TGGC is Benign according to our data. Variant chr1-151612258-T-TGGC is described in ClinVar as [Benign]. Clinvar id is 462816.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00425 (645/151608) while in subpopulation NFE AF= 0.00579 (393/67830). AF 95% confidence interval is 0.00532. There are 2 homozygotes in gnomad4. There are 345 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 645 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX27	NM_001330723.2	c.69_71dup	p.Gly24dup	inframe_insertion	1/12	ENST00000458013.7
LOC124904420	XR_007066622.1	n.319_320insGCC		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX27	ENST00000458013.7	c.69_71dup	p.Gly24dup	inframe_insertion	1/12	5	NM_001330723.2	P1
	ENST00000504583.2	n.314_315insGCC		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes AF: 0.00426 AC: 645 AN: 151502 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000995

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000918

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.0169

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00579

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.00373 AC: 178 AN: 47704 Hom.: 1 AF XY: 0.00342 AC XY: 93 AN XY: 27186

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000743

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00109

Gnomad FIN exome AF: 0.0120

Gnomad NFE exome AF: 0.00301

Gnomad OTH exome AF: 0.00600

GnomAD4 exome AF: 0.00421 AC: 5420 AN: 1288822 Hom.: 14 Cov.: 31 AF XY: 0.00423 AC XY: 2675 AN XY: 632138

Gnomad4 AFR exome AF: 0.000537

Gnomad4 AMR exome AF: 0.000966

Gnomad4 ASJ exome AF: 0.00325

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00125

Gnomad4 FIN exome AF: 0.0147

Gnomad4 NFE exome AF: 0.00430

Gnomad4 OTH exome AF: 0.00335

GnomAD4 genome AF: 0.00425 AC: 645 AN: 151608 Hom.: 2 Cov.: 32 AF XY: 0.00466 AC XY: 345 AN XY: 74098

Gnomad4 AFR AF: 0.000992

Gnomad4 AMR AF: 0.000917

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.0169

Gnomad4 NFE AF: 0.00579

Gnomad4 OTH AF: 0.000950

Bravo AF: 0.00306

Asia WGS AF: 0.000870 AC: 3 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Severe myoclonic epilepsy in infancy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs567208173; hg19: chr1-151584734;