NM_001080437.3:c.675C>T

Variant names:

• chr2-241034600-C-T
• rs751474096
• NM_001080437.3:c.675C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001080437.3(SNED1):​c.675C>T​(p.Tyr225Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,520 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SNED1 NM_001080437.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.33
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-241034600-C-T is Benign according to our data. Variant chr2-241034600-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2652104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.33 with no splicing effect.

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.675C>T	p.Tyr225Tyr	synonymous	Exon 4 of 32	NP_001073906.1	Q8TER0-1
	SNED1-AS1	NR_187211.1		n.40-997G>A		intron	N/A
	SNED1-AS1	NR_187212.1		n.40-997G>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.675C>T	p.Tyr225Tyr	synonymous	Exon 4 of 32	ENSP00000308893.8	Q8TER0-1
	SNED1	ENST00000957411.1		c.675C>T	p.Tyr225Tyr	synonymous	Exon 4 of 32	ENSP00000627470.1
	SNED1	ENST00000957409.1		c.675C>T	p.Tyr225Tyr	synonymous	Exon 4 of 31	ENSP00000627468.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000408 AC: 1 AN: 245208 AF XY: 0.00000748

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: 0.00

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458520 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725346

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 86084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110688

Other (OTH) AF: 0.0000166 AC: 1 AN: 60260

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs751474096; hg19: chr2-241974017;