Variant chr2-241033850-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080437.3(SNED1):c.617C>T(p.Thr206Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,624 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.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SNED1
NM_001080437.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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 links:

SNED1 (HGNC:):

SNED1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21794826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNED1	NM_001080437.3 linkuse as main transcript	c.617C>T	p.Thr206Ile	missense_variant	3/32	ENST00000310397.13	NP_001073906.1	Q8TER0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SNED1	ENST00000310397.13 linkuse as main transcript	c.617C>T	p.Thr206Ile	missense_variant	3/32	5	NM_001080437.3	ENSP00000308893.8	Q8TER0-1
SNED1	ENST00000405547.7 linkuse as main transcript	c.617C>T	p.Thr206Ile	missense_variant	3/30	5		ENSP00000386007.3	Q8TER0-3
SNED1	ENST00000401884.5 linkuse as main transcript	c.617C>T	p.Thr206Ile	missense_variant	3/27	5		ENSP00000384871.1	Q8TER0-5
SNED1-AS1	ENST00000458377.1 linkuse as main transcript	n.38-247G>A		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000423

AC:

AN:

236266

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000575

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454624

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722946

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.617C>T (p.T206I) alteration is located in exon 3 (coding exon 3) of the SNED1 gene. This alteration results from a C to T substitution at nucleotide position 617, causing the threonine (T) at amino acid position 206 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

0.15

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.84

T;T;T

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.8

M;M;M

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.017

D;T;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

0.38

.;.;B

Vest4

0.21

MutPred

0.62

Loss of disorder (P = 0.0484);Loss of disorder (P = 0.0484);Loss of disorder (P = 0.0484);

MVP

0.11

MPC

0.77

ClinPred

0.23

GERP RS

0.15

Varity_R

0.061

gMVP

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over