2-241030510-C-T

Variant summary

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

The NM_001080437.3(SNED1):​c.440C>T​(p.Thr147Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T147N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

SNED1
NM_001080437.3 missense

Scores

12
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53
Variant links:
Genes affected
SNED1 (HGNC:24696): (sushi, nidogen and EGF like domains 1) Predicted to enable Notch binding activity. Predicted to be involved in cell-matrix adhesion. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]
SNED1-AS1 (HGNC:41060): (SNED1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
SNED1NM_001080437.3 linkc.440C>T p.Thr147Ile missense_variant Exon 2 of 32 ENST00000310397.13 NP_001073906.1 Q8TER0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNED1ENST00000310397.13 linkc.440C>T p.Thr147Ile missense_variant Exon 2 of 32 5 NM_001080437.3 ENSP00000308893.8 Q8TER0-1
SNED1ENST00000405547.7 linkc.440C>T p.Thr147Ile missense_variant Exon 2 of 30 5 ENSP00000386007.3 Q8TER0-3
SNED1ENST00000401884.5 linkc.440C>T p.Thr147Ile missense_variant Exon 2 of 27 5 ENSP00000384871.1 Q8TER0-5
SNED1-AS1ENST00000458377.1 linkn.140+2991G>A intron_variant Intron 2 of 2 4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248650
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135096
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000889
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.440C>T (p.T147I) alteration is located in exon 2 (coding exon 2) of the SNED1 gene. This alteration results from a C to T substitution at nucleotide position 440, causing the threonine (T) at amino acid position 147 to be replaced by an isoleucine (I). 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
Benign
0.25
BayesDel_addAF
Uncertain
0.081
D
BayesDel_noAF
Benign
-0.12
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
.;.;T
Eigen
Uncertain
0.33
Eigen_PC
Benign
0.20
FATHMM_MKL
Benign
0.40
N
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.55
D;D;D
MetaSVM
Uncertain
0.37
D
MutationAssessor
Uncertain
2.8
M;M;M
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-2.6
D;D;D
REVEL
Uncertain
0.48
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
0.99
.;.;D
Vest4
0.52
MutPred
0.56
Loss of catalytic residue at F150 (P = 0.0725);Loss of catalytic residue at F150 (P = 0.0725);Loss of catalytic residue at F150 (P = 0.0725);
MVP
0.66
MPC
0.51
ClinPred
0.79
D
GERP RS
3.5
Varity_R
0.13
gMVP
0.68

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs575768806; hg19: chr2-241969927; API