16-11676310-C-G

Variant names:

• chr16-11676310-C-G
• rs768584522
• NM_003498.6:c.251C>G

Variant summary

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

The NM_003498.6(SNN):​c.251C>G​(p.Pro84Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P84A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SNN NM_003498.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.88
• Publications: 0 publications found

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

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=0.16261685).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003498.6. 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
	SNN	NM_003498.6	MANE Select	c.251C>G	p.Pro84Arg	missense	Exon 2 of 2	NP_003489.1	O75324

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNN	ENST00000329565.6	TSL:1 MANE Select	c.251C>G	p.Pro84Arg	missense	Exon 2 of 2	ENSP00000329287.5	O75324
	SNN	ENST00000907333.1		c.251C>G	p.Pro84Arg	missense	Exon 3 of 3	ENSP00000577392.1
	SNN	ENST00000907334.1		c.251C>G	p.Pro84Arg	missense	Exon 2 of 2	ENSP00000577393.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460804 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726510

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111228

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.88
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PhyloP100		4.9
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.089
Sift	Benign	0.037	D
Sift4G	Benign	0.15	T
Polyphen		0.019	B
Vest4		0.17
MutPred		0.48		Gain of MoRF binding (P = 4e-04)
MVP		0.040
MPC		0.87
ClinPred		0.53	D
GERP RS		4.5
Varity_R		0.22
gMVP		0.68
Mutation Taster		=62/38	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

Other links and lift over

dbSNP: rs768584522; hg19: chr16-11770166;