NM_000450.2:c.975C>A

Variant names:

• chr1-169729301-G-T
• rs79478039
• NM_000450.2:c.975C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000450.2(SELE):​c.975C>A​(p.Phe325Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,614,124 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (32 hom.)
• Consequence: SELE NM_000450.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.100
• Publications: 6 publications found

Genes affected

SELE (HGNC:10718): (selectin E) The protein encoded by this gene is found in cytokine-stimulated endothelial cells and is thought to be responsible for the accumulation of blood leukocytes at sites of inflammation by mediating the adhesion of cells to the vascular lining. It exhibits structural features such as the presence of lectin- and EGF-like domains followed by short consensus repeat (SCR) domains that contain 6 conserved cysteine residues. These proteins are part of the selectin family of cell adhesion molecules. Adhesion molecules participate in the interaction between leukocytes and the endothelium and appear to be involved in the pathogenesis of atherosclerosis. [provided by RefSeq, Jul 2008]

FIRRM (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0082035065).
• BS2: High Homozygotes in GnomAdExome4 at 32 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000450.2. 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
	SELE	NM_000450.2	MANE Select	c.975C>A	p.Phe325Leu	missense	Exon 7 of 14	NP_000441.2	P16581

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELE	ENST00000333360.12	TSL:1 MANE Select	c.975C>A	p.Phe325Leu	missense	Exon 7 of 14	ENSP00000331736.7	P16581
	SELE	ENST00000367776.5	TSL:5	c.975C>A	p.Phe325Leu	missense	Exon 6 of 12	ENSP00000356750.1	Q5TI73
	SELE	ENST00000367777.5	TSL:5	c.975C>A	p.Phe325Leu	missense	Exon 6 of 12	ENSP00000356751.1	Q5TI74

Frequencies

GnomAD3 genomes AF: 0.00323 AC: 492 AN: 152210 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000699

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00485

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00352 AC: 884 AN: 250902 AF XY: 0.00365

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00286

Gnomad ASJ exome AF: 0.00756

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00162

Gnomad NFE exome AF: 0.00423

Gnomad OTH exome AF: 0.00474

GnomAD4 exome AF: 0.00402 AC: 5876 AN: 1461796 Hom.: 32 Cov.: 32 AF XY: 0.00395 AC XY: 2876 AN XY: 727192

African (AFR) AF: 0.000478 AC: 16 AN: 33476

American (AMR) AF: 0.00277 AC: 124 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00754 AC: 197 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39674

South Asian (SAS) AF: 0.00526 AC: 454 AN: 86256

European-Finnish (FIN) AF: 0.00154 AC: 82 AN: 53404

Middle Eastern (MID) AF: 0.00746 AC: 43 AN: 5766

European-Non Finnish (NFE) AF: 0.00423 AC: 4704 AN: 1111974

Other (OTH) AF: 0.00422 AC: 255 AN: 60390

GnomAD4 genome AF: 0.00322 AC: 491 AN: 152328 Hom.: 1 Cov.: 32 AF XY: 0.00293 AC XY: 218 AN XY: 74498

African (AFR) AF: 0.000697 AC: 29 AN: 41586

American (AMR) AF: 0.00431 AC: 66 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00456 AC: 22 AN: 4824

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00485 AC: 330 AN: 68022

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00427 Hom.: 4

Bravo AF: 0.00322

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00488 AC: 42

ExAC AF: 0.00333 AC: 404

Asia WGS AF: 0.00173 AC: 6 AN: 3476

EpiCase AF: 0.00605

EpiControl AF: 0.00510

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.95
DANN	Benign	0.86
DEOGEN2	Benign	0.060	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.0082	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.10
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.20
Sift	Benign	0.10	T
Sift4G	Benign	0.14	T
Polyphen		0.10	B
Vest4		0.14
MutPred		0.64		Gain of ubiquitination at K328 (P = 0.0843)
MVP		0.71
MPC		0.072
ClinPred		0.027	T
GERP RS		-4.1
gMVP		0.83
Mutation Taster		=99/1	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: rs79478039; hg19: chr1-169698442;