rs111343679

Variant names:

• chr3-63663967-A-C
• rs111343679
• NM_001080537.2:c.316A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-63663967-A-C
• chr3-63663967-A-G
• chr3-63663967-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080537.2(SNTN):​c.316A>C​(p.Ile106Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. I106F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SNTN NM_001080537.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619
• Publications: 0 publications found

Genes affected

SNTN (HGNC:33706): (sentan, cilia apical structure protein) Predicted to enable calcium ion binding activity and calcium-dependent protein binding activity. Predicted to be located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050676525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTN	NM_001080537.2	c.316A>C	p.Ile106Leu	missense_variant	Exon 4 of 4	ENST00000343837.8	NP_001074006.1
SNTN	NM_001348756.2	c.406A>C	p.Ile136Leu	missense_variant	Exon 5 of 5		NP_001335685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTN	ENST00000343837.8	c.316A>C	p.Ile106Leu	missense_variant	Exon 4 of 4	2	NM_001080537.2	ENSP00000341442.3
SNTN	ENST00000469440.5	c.406A>C	p.Ile136Leu	missense_variant	Exon 5 of 5	3		ENSP00000420078.1
SNTN	ENST00000496807.1	c.273+4103A>C		intron_variant	Intron 3 of 3	4		ENSP00000419971.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460980 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726670

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 85822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111790

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.80
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.53	N;.
PhyloP100		0.62
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.034
Sift	Benign	0.49	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;.
Vest4		0.12
MutPred		0.34		Gain of glycosylation at S108 (P = 0.0188);.;
MVP		0.014
MPC		0.022
ClinPred		0.098	T
GERP RS		0.33
Varity_R		0.070
gMVP		0.32
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs111343679; hg19: chr3-63649643;