chr5-123001955-G-C

Position:

• chr5-123001955-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014035.4(SNX24):​c.393G>C​(p.Gln131His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX24 NM_014035.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.29

Genes affected

SNX24 (HGNC:21533): (sorting nexin 24) Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to be involved in protein transport. Predicted to be located in cytoplasmic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34103918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX24	NM_014035.4	c.393G>C	p.Gln131His	missense_variant	6/7	ENST00000261369.9	NP_054754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX24	ENST00000261369.9	c.393G>C	p.Gln131His	missense_variant	6/7	1	NM_014035.4	ENSP00000261369.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.393G>C (p.Q131H) alteration is located in exon 6 (coding exon 6) of the SNX24 gene. This alteration results from a G to C substitution at nucleotide position 393, causing the glutamine (Q) at amino acid position 131 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.0097	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T;.;T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.92	D;.;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.6	L;L;.;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.3	N;N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.99	D;D;.;D
Vest4		0.31
MutPred		0.48		Gain of glycosylation at S126 (P = 0.1382);Gain of glycosylation at S126 (P = 0.1382);.;Gain of glycosylation at S126 (P = 0.1382);
MVP		0.80
MPC		0.52
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.37
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-122337650;