16-11676099-A-T

Variant names:

• chr16-11676099-A-T
• NM_003498.6:c.40A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003498.6(SNN):​c.40A>T​(p.Thr14Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNN NM_003498.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81

Genes affected

SNN (HGNC:11149): (stannin) Enables metal ion binding activity. Predicted to be involved in response to toxic substance. Located in cytoplasm. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNN	NM_003498.6	c.40A>T	p.Thr14Ser	missense_variant	Exon 2 of 2	ENST00000329565.6	NP_003489.1
SNN	XM_017023741.2	c.178A>T	p.Thr60Ser	missense_variant	Exon 2 of 2		XP_016879230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNN	ENST00000329565.6	c.40A>T	p.Thr14Ser	missense_variant	Exon 2 of 2	1	NM_003498.6	ENSP00000329287.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.40A>T (p.T14S) alteration is located in exon 2 (coding exon 1) of the SNN gene. This alteration results from a A to T substitution at nucleotide position 40, causing the threonine (T) at amino acid position 14 to be replaced by a serine (S). 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	0.73
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	-0.19	T
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.026	D
Sift4G	Benign	0.16	T
Polyphen		0.94	P
Vest4		0.71
MutPred		0.57		Gain of glycosylation at T14 (P = 0.0291);
MVP		0.35
MPC		1.7
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.62
gMVP		0.95

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-11769955;