rs541477246

Variant names:

• chr2-241034721-G-A
• rs541477246
• NM_001080437.3:c.796G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-241034721-G-A
• chr2-241034721-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001080437.3(SNED1):​c.796G>A​(p.Gly266Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,565,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: SNED1 NM_001080437.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032165945).

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.796G>A	p.Gly266Ser	missense	Exon 4 of 32	NP_001073906.1	Q8TER0-1
	SNED1-AS1	NR_187211.1		n.40-1118C>T		intron	N/A
	SNED1-AS1	NR_187212.1		n.40-1118C>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.796G>A	p.Gly266Ser	missense	Exon 4 of 32	ENSP00000308893.8	Q8TER0-1
	SNED1	ENST00000957411.1		c.796G>A	p.Gly266Ser	missense	Exon 4 of 32	ENSP00000627470.1
	SNED1	ENST00000957409.1		c.796G>A	p.Gly266Ser	missense	Exon 4 of 31	ENSP00000627468.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000919 AC: 16 AN: 174138 AF XY: 0.0000961

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000115

Gnomad ASJ exome AF: 0.000120

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000958

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000105 AC: 148 AN: 1413484 Hom.: 0 Cov.: 31 AF XY: 0.000107 AC XY: 75 AN XY: 698186

African (AFR) AF: 0.000216 AC: 7 AN: 32348

American (AMR) AF: 0.000186 AC: 7 AN: 37656

Ashkenazi Jewish (ASJ) AF: 0.0000399 AC: 1 AN: 25068

East Asian (EAS) AF: 0.00 AC: 0 AN: 37124

South Asian (SAS) AF: 0.0000374 AC: 3 AN: 80150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49108

Middle Eastern (MID) AF: 0.000882 AC: 5 AN: 5672

European-Non Finnish (NFE) AF: 0.000101 AC: 110 AN: 1087716

Other (OTH) AF: 0.000256 AC: 15 AN: 58642

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152314 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74482

African (AFR) AF: 0.0000722 AC: 3 AN: 41560

American (AMR) AF: 0.000196 AC: 3 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000123 Hom.: 0

Bravo AF: 0.000136

ExAC AF: 0.0000339 AC: 4

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	0.062
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.55	N
PhyloP100		3.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.15
Sift	Benign	0.70	T
Sift4G	Benign	0.65	T
Polyphen		0.0070	B
Vest4		0.25
MVP		0.082
MPC		0.39
ClinPred		0.036	T
GERP RS		0.89
Varity_R		0.036
gMVP		0.55
Mutation Taster		=89/11	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: rs541477246; hg19: chr2-241974138; COSMIC: COSV100123686; COSMIC: COSV100123686;