rs781269445

Variant names:

• chr1-98685065-A-G
• rs781269445
• NM_015976.5:c.361A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-98685065-A-G
• chr1-98685065-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015976.5(SNX7):​c.361A>G​(p.Lys121Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000701 in 1,468,746 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: SNX7 NM_015976.5 missense, splice_region
• Scores: Splicing: ADA: 0.006206
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.52
• Publications: 0 publications found

Genes affected

SNX7 (HGNC:14971): (sorting nexin 7) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region like some family members, and its exact function is unknown. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015976.5. 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
	SNX7	NM_015976.5	MANE Select	c.361A>G	p.Lys121Glu	missense splice_region	Exon 2 of 9	NP_057060.2	Q9UNH6-3
	SNX7	NM_152238.4		c.361A>G	p.Lys121Glu	missense splice_region	Exon 2 of 8	NP_689424.2	E9PNL2
	SNX7	NM_001364903.1		c.169A>G	p.Lys57Glu	missense splice_region	Exon 3 of 10	NP_001351832.1	Q9UNH6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX7	ENST00000306121.8	TSL:1 MANE Select	c.361A>G	p.Lys121Glu	missense splice_region	Exon 2 of 9	ENSP00000304429.3	Q9UNH6-3
	SNX7	ENST00000528824.1	TSL:1	n.*181A>G		splice_region non_coding_transcript_exon	Exon 3 of 9	ENSP00000435172.1	E9PLE1
	SNX7	ENST00000528824.1	TSL:1	n.*181A>G		3_prime_UTR	Exon 3 of 9	ENSP00000435172.1	E9PLE1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000309 AC: 6 AN: 194282 AF XY: 0.0000283

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: 0.0000629

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000737 AC: 97 AN: 1316552 Hom.: 0 Cov.: 26 AF XY: 0.0000543 AC XY: 35 AN XY: 644208

African (AFR) AF: 0.0000340 AC: 1 AN: 29454

American (AMR) AF: 0.00 AC: 0 AN: 31268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21826

East Asian (EAS) AF: 0.00 AC: 0 AN: 36454

South Asian (SAS) AF: 0.00 AC: 0 AN: 58946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5198

European-Non Finnish (NFE) AF: 0.0000873 AC: 90 AN: 1030856

Other (OTH) AF: 0.000112 AC: 6 AN: 53482

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74338

African (AFR) AF: 0.0000482 AC: 2 AN: 41456

American (AMR) AF: 0.000131 AC: 2 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000684 Hom.: 0

Bravo AF: 0.0000453

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.0	T
PhyloP100		6.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.68
MutPred		0.53		Loss of ubiquitination at K121 (P = 0.027)
MVP		0.56
MPC		0.31
ClinPred		0.83	D
GERP RS		4.3
gMVP		0.69
Mutation Taster		=18/82	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0062
dbscSNV1_RF	Benign	0.020
SpliceAI score (max)		0.050		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: rs781269445; hg19: chr1-99150621;