1-98691172-C-G

Variant names:

• chr1-98691172-C-G
• rs1651100975
• NM_015976.5:c.461C>G

Variant summary

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

The NM_015976.5(SNX7):​c.461C>G​(p.Thr154Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,880 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T154I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SNX7 NM_015976.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• 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.461C>G	p.Thr154Ser	missense	Exon 3 of 9	NP_057060.2	Q9UNH6-3
	SNX7	NM_152238.4		c.461C>G	p.Thr154Ser	missense	Exon 3 of 8	NP_689424.2	E9PNL2
	SNX7	NM_001364903.1		c.269C>G	p.Thr90Ser	missense	Exon 4 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.461C>G	p.Thr154Ser	missense	Exon 3 of 9	ENSP00000304429.3	Q9UNH6-3
	SNX7	ENST00000528824.1	TSL:1	n.*281C>G		non_coding_transcript_exon	Exon 4 of 9	ENSP00000435172.1	E9PLE1
	SNX7	ENST00000528824.1	TSL:1	n.*281C>G		3_prime_UTR	Exon 4 of 9	ENSP00000435172.1	E9PLE1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453880 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723344

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33044

American (AMR) AF: 0.00 AC: 0 AN: 43932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25874

East Asian (EAS) AF: 0.00 AC: 0 AN: 39270

South Asian (SAS) AF: 0.00 AC: 0 AN: 85130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107736

Other (OTH) AF: 0.00 AC: 0 AN: 59962

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.78	T
PhyloP100		7.9
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.29
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.040	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.37		Gain of disorder (P = 0.0239)
MVP		0.65
MPC		0.36
ClinPred		0.99	D
GERP RS		6.0
gMVP		0.37
Mutation Taster		=40/60	disease causing

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: rs1651100975; hg19: chr1-99156728;