rs575768806

Variant names:

• chr2-241030510-C-A
• rs575768806
• NM_001080437.3:c.440C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-241030510-C-A
• chr2-241030510-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080437.3(SNED1):​c.440C>A​(p.Thr147Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. T147I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SNED1 NM_001080437.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30832353).

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.440C>A	p.Thr147Asn	missense	Exon 2 of 32	NP_001073906.1	Q8TER0-1
	SNED1-AS1	NR_187211.1		n.142+2991G>T		intron	N/A
	SNED1-AS1	NR_187212.1		n.142+2991G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNED1	ENST00000310397.13	TSL:5 MANE Select	c.440C>A	p.Thr147Asn	missense	Exon 2 of 32	ENSP00000308893.8	Q8TER0-1
	SNED1	ENST00000957411.1		c.440C>A	p.Thr147Asn	missense	Exon 2 of 32	ENSP00000627470.1
	SNED1	ENST00000957409.1		c.440C>A	p.Thr147Asn	missense	Exon 2 of 31	ENSP00000627468.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248650 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461590 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727064

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152354 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74514

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.15
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.041	D
MutationAssessor	Benign	1.9	L
PhyloP100		1.5
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.015	D
Polyphen		0.99	D
Vest4		0.38
MutPred		0.56		Loss of stability (P = 0.1483)
MVP		0.54
MPC		0.70
ClinPred		0.39	T
GERP RS		3.5
Varity_R		0.14
gMVP		0.72
Mutation Taster		=70/30	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: rs575768806; hg19: chr2-241969927;