NM_014426.4:c.1195G>T

Variant names:

• chr20-17942377-C-A
• NM_014426.4:c.1195G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014426.4(SNX5):​c.1195G>T​(p.Asp399Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,950 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SNX5 NM_014426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.73

Genes affected

SNX5 (HGNC:14969): (sorting nexin 5) 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 functions in endosomal sorting, the phosphoinositide-signaling pathway, and macropinocytosis. This gene may play a role in the tumorigenesis of papillary thyroid carcinoma. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX5	NM_014426.4	c.1195G>T	p.Asp399Tyr	missense_variant	Exon 13 of 13	ENST00000377759.9	NP_055241.1
SNX5	NM_152227.3	c.1195G>T	p.Asp399Tyr	missense_variant	Exon 14 of 14		NP_689413.1
SNX5	NM_001282454.2	c.880G>T	p.Asp294Tyr	missense_variant	Exon 13 of 13		NP_001269383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX5	ENST00000377759.9	c.1195G>T	p.Asp399Tyr	missense_variant	Exon 13 of 13	1	NM_014426.4	ENSP00000366988.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458950 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 726006

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.27
Sift	Benign	0.032	D;D
Sift4G	Uncertain	0.038	D;D
Polyphen		0.94	P;P
Vest4		0.45
MutPred		0.60		Loss of disorder (P = 0.0524);Loss of disorder (P = 0.0524);
MVP		0.65
MPC		0.26
ClinPred		0.89	D
GERP RS		4.8
Varity_R		0.14
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr20-17923021;