chr3-63664072-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. 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. 16/22 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
• Publications: 1 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 -6 ACMG points.

• 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 VariationId is 2457786.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080537.2. 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
	SNTN	NM_001080537.2	MANE Select	c.421C>T	p.Arg141Trp	missense	Exon 4 of 4	NP_001074006.1	A6NMZ2
	SNTN	NM_001348756.2		c.511C>T	p.Arg171Trp	missense	Exon 5 of 5	NP_001335685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTN	ENST00000343837.8	TSL:2 MANE Select	c.421C>T	p.Arg141Trp	missense	Exon 4 of 4	ENSP00000341442.3	A6NMZ2
	SNTN	ENST00000496807.1	TSL:4	c.273+4208C>T		intron	N/A	ENSP00000419971.1	C9JXY5
	SNTN	ENST00000469440.5	TSL:3	c.*12C>T		downstream_gene	N/A	ENSP00000420078.1	C9JRU3

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

GnomAD2 exomes AF: 0.0000693 AC: 17 AN: 245260 AF XY: 0.0000453

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 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

African (AFR) AF: 0.0000301 AC: 1 AN: 33214

American (AMR) AF: 0.0000917 AC: 4 AN: 43630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.0000759 AC: 3 AN: 39540

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1109840

Other (OTH) AF: 0.00 AC: 0 AN: 60166

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

African (AFR) AF: 0.0000724 AC: 3 AN: 41414

American (AMR) AF: 0.00118 AC: 18 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000878 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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.2
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
Mutation Taster		=94/6	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: rs147825012; hg19: chr3-63649748; COSMIC: COSV106506882; COSMIC: COSV106506882;