2-241033850-C-T

Variant names:

• chr2-241033850-C-T
• rs1434194147
• NM_001080437.3:c.617C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SNED1 NM_001080437.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19

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)

ACMG classification

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 rank	MANE	Protein	UniProt
SNED1	NM_001080437.3	c.617C>T	p.Thr206Ile	missense_variant	Exon 3 of 32	ENST00000310397.13	NP_001073906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNED1	ENST00000310397.13	c.617C>T	p.Thr206Ile	missense_variant	Exon 3 of 32	5	NM_001080437.3	ENSP00000308893.8
SNED1	ENST00000405547.7	c.617C>T	p.Thr206Ile	missense_variant	Exon 3 of 30	5		ENSP00000386007.3
SNED1	ENST00000401884.5	c.617C>T	p.Thr206Ile	missense_variant	Exon 3 of 27	5		ENSP00000384871.1
SNED1-AS1	ENST00000458377.1	n.38-247G>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000423 AC: 1 AN: 236266 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 128616

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: 1 AN: 1454624 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722946

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.: 33

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	.;.;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.84	T;T;T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.8	M;M;M
PrimateAI	Benign	0.36	T
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	T
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

Other links and lift over

dbSNP: rs1434194147; hg19: chr2-241973267;