16-11676199-A-C

Variant names:

• chr16-11676199-A-C
• NM_003498.6:c.140A>C

Variant summary

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

The NM_003498.6(SNN):​c.140A>C​(p.Glu47Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNN NM_003498.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.68

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 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
SNN	NM_003498.6	c.140A>C	p.Glu47Ala	missense_variant	Exon 2 of 2	ENST00000329565.6	NP_003489.1
SNN	XM_017023741.2	c.278A>C	p.Glu93Ala	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.140A>C	p.Glu47Ala	missense_variant	Exon 2 of 2	1	NM_003498.6	ENSP00000329287.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.140A>C (p.E47A) alteration is located in exon 2 (coding exon 1) of the SNN gene. This alteration results from a A to C substitution at nucleotide position 140, causing the glutamic acid (E) at amino acid position 47 to be replaced by an alanine (A). 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	Uncertain	0.51
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.096	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.70	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.94	P
Vest4		0.65
MutPred		0.70		Loss of sheet (P = 0.0126);
MVP		0.13
MPC		1.8
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.81
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: chr16-11770055;