chr1-98661820-C-T

Variant names:

• chr1-98661820-C-T
• rs1423862936
• NM_015976.5:c.89C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015976.5(SNX7):​c.89C>T​(p.Pro30Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000241 in 1,245,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: SNX7 NM_015976.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11736041).

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.89C>T	p.Pro30Leu	missense	Exon 1 of 9	NP_057060.2	Q9UNH6-3
	SNX7	NM_152238.4		c.89C>T	p.Pro30Leu	missense	Exon 1 of 8	NP_689424.2	E9PNL2
	SNX7	NM_001364903.1		c.-224C>T		5_prime_UTR	Exon 1 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.89C>T	p.Pro30Leu	missense	Exon 1 of 9	ENSP00000304429.3	Q9UNH6-3
	SNX7	ENST00000971618.1		c.89C>T	p.Pro30Leu	missense	Exon 1 of 9	ENSP00000641677.1
	SNX7	ENST00000851356.1		c.89C>T	p.Pro30Leu	missense	Exon 1 of 9	ENSP00000521415.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152010 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1093846 Hom.: 0 Cov.: 29 AF XY: 0.00000194 AC XY: 1 AN XY: 516484

African (AFR) AF: 0.0000437 AC: 1 AN: 22904

American (AMR) AF: 0.00 AC: 0 AN: 8376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14328

East Asian (EAS) AF: 0.00 AC: 0 AN: 26482

South Asian (SAS) AF: 0.00 AC: 0 AN: 19486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36294

Middle Eastern (MID) AF: 0.000336 AC: 1 AN: 2976

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 919324

Other (OTH) AF: 0.00 AC: 0 AN: 43676

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152010 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74246

African (AFR) AF: 0.0000242 AC: 1 AN: 41394

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

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	Benign	0.089
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.6
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.042
Sift	Uncertain	0.013	D
Sift4G	Benign	0.092	T
Polyphen		0.15	B
Vest4		0.18
MutPred		0.27		Gain of sheet (P = 0.0125)
MVP		0.28
MPC		0.48
ClinPred		0.93	D
GERP RS		4.6
PromoterAI		0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.26
Mutation Taster		=77/23	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: rs1423862936; hg19: chr1-99127376;