SNX4 p.Ser448Arg

Variant names:

• chr3-125447790-T-G
• NM_003794.4:c.1342A>C
• SNX4 p.Ser448Arg

Your query was ambiguous. Multiple possible variants found:

• chr3-125447790-T-G
• chr3-125447788-G-T
• chr3-125447788-G-C
• chr3-125447788-GCT-ACG
• chr3-125447788-GCT-TCG
• chr3-125447788-GCT-CCG

Variant summary

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

The NM_003794.4(SNX4):​c.1342A>C​(p.Ser448Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX4 NM_003794.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 0 publications found

Genes affected

SNX4 (HGNC:11175): (sorting nexin 4) 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 associated with the long isoform of the leptin receptor and with receptor tyrosine kinases for platelet-derived growth factor, insulin, and epidermal growth factor in cell cultures, but its function is unknown. This protein may form oligomeric complexes with family members. Two transcript variants, one protein coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Nov 2012]

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=0.15442744).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003794.4. 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
	SNX4	NM_003794.4	MANE Select	c.1342A>C	p.Ser448Arg	missense	Exon 14 of 14	NP_003785.1	O95219-1
	SNX4	NR_073435.2		n.1250A>C		non_coding_transcript_exon	Exon 13 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX4	ENST00000251775.9	TSL:1 MANE Select	c.1342A>C	p.Ser448Arg	missense	Exon 14 of 14	ENSP00000251775.4	O95219-1
	SNX4	ENST00000873377.1		c.1465A>C	p.Ser489Arg	missense	Exon 15 of 15	ENSP00000543436.1
	SNX4	ENST00000873378.1		c.1459A>C	p.Ser487Arg	missense	Exon 16 of 16	ENSP00000543437.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.5
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.050
Sift	Benign	0.14	T
Sift4G	Benign	0.39	T
Varity_R		0.086
gMVP		0.22
Mutation Taster		=92/8	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-125166634;