2-241030408-C-T

Variant names:

• chr2-241030408-C-T
• rs375938996
• NM_001080437.3:c.338C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001080437.3(SNED1):​c.338C>T​(p.Ala113Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A113G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNED1 NM_001080437.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.68
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080437.3. 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
	SNED1	NM_001080437.3	MANE Select	c.338C>T	p.Ala113Val	missense	Exon 2 of 32	NP_001073906.1	Q8TER0-1
	SNED1-AS1	NR_187211.1		n.142+3093G>A		intron	N/A
	SNED1-AS1	NR_187212.1		n.142+3093G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNED1	ENST00000310397.13	TSL:5 MANE Select	c.338C>T	p.Ala113Val	missense	Exon 2 of 32	ENSP00000308893.8	Q8TER0-1
	SNED1	ENST00000957411.1		c.338C>T	p.Ala113Val	missense	Exon 2 of 32	ENSP00000627470.1
	SNED1	ENST00000957409.1		c.338C>T	p.Ala113Val	missense	Exon 2 of 31	ENSP00000627468.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.44		Gain of sheet (P = 0.0043)
MVP		0.60
MPC		1.2
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.15
gMVP		0.68
Mutation Taster		=73/27	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: rs375938996; hg19: chr2-241969825;