3-63664072-C-T

Variant names:

• chr3-63664072-C-T
• rs147825012
• NM_001080537.2:c.421C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001080537.2(SNTN):​c.421C>T​(p.Arg141Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,608,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R141Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: SNTN NM_001080537.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027613103).
• BP6: Variant 3-63664072-C-T is Benign according to our data. Variant chr3-63664072-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2457786.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTN	NM_001080537.2	c.421C>T	p.Arg141Trp	missense_variant	Exon 4 of 4	ENST00000343837.8	NP_001074006.1
SNTN	NM_001348756.2	c.511C>T	p.Arg171Trp	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.421C>T	p.Arg141Trp	missense_variant	Exon 4 of 4	2	NM_001080537.2	ENSP00000341442.3
SNTN	ENST00000496807.1	c.273+4208C>T		intron_variant	Intron 3 of 3	4		ENSP00000419971.1
SNTN	ENST00000469440.5	c.*12C>T		downstream_gene_variant		3		ENSP00000420078.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152062 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000693 AC: 17 AN: 245260 Hom.: 0 AF XY: 0.0000453 AC XY: 6 AN XY: 132344

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.0000900

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000552

Gnomad SAS exome AF: 0.0000348

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000896

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000234 AC: 34 AN: 1456006 Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14 AN XY: 723974

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.0000917

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000759

Gnomad4 SAS exome AF: 0.0000236

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152062 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74264

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000308 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.00

EpiControl AF: 0.0000596

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 17, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.10
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.6	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.038
Sift	Benign	0.31	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.090
MVP		0.048
MPC		0.022
ClinPred		0.12	T
GERP RS		2.0
Varity_R		0.040
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs147825012; hg19: chr3-63649748;