NM_000655.5:c.577T>C

Variant names:

• chr1-169707345-A-G
• rs1131498
• NM_000655.5:c.577T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000655.5(SELL):​c.577T>C​(p.Phe193Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,607,898 control chromosomes in the GnomAD database, including 51,524 homozygotes. In-silico tool predicts a benign outcome for this variant. 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. F193Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.21 (3854 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47670 hom.)
• Consequence: SELL NM_000655.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 38 publications found

Genes affected

SELL (HGNC:10720): (selectin L) This gene encodes a cell surface adhesion molecule that belongs to a family of adhesion/homing receptors. The encoded protein contains a C-type lectin-like domain, a calcium-binding epidermal growth factor-like domain, and two short complement-like repeats. The gene product is required for binding and subsequent rolling of leucocytes on endothelial cells, facilitating their migration into secondary lymphoid organs and inflammation sites. Single-nucleotide polymorphisms in this gene have been associated with various diseases including immunoglobulin A nephropathy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2009]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014271736).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000655.5. 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
	SELL	NM_000655.5	MANE Select	c.577T>C	p.Phe193Leu	missense	Exon 4 of 9	NP_000646.3	P14151-1
	SELL	NR_029467.2		n.546T>C		non_coding_transcript_exon	Exon 2 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELL	ENST00000236147.6	TSL:1 MANE Select	c.577T>C	p.Phe193Leu	missense	Exon 4 of 9	ENSP00000236147.5	P14151-1
	SELL	ENST00000463108.5	TSL:1	n.777T>C		non_coding_transcript_exon	Exon 4 of 7
	SELL	ENST00000650983.1		c.616T>C	p.Phe206Leu	missense	Exon 4 of 9	ENSP00000498227.1	P14151-2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32356 AN: 151898 Hom.: 3855 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.00502

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.227

GnomAD2 exomes AF: 0.206 AC: 50921 AN: 247268 AF XY: 0.211

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.129

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.00549

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.249 AC: 361860 AN: 1455882 Hom.: 47670 Cov.: 29 AF XY: 0.247 AC XY: 179173 AN XY: 724332

African (AFR) AF: 0.150 AC: 4980 AN: 33308

American (AMR) AF: 0.136 AC: 6054 AN: 44448

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 6993 AN: 25992

East Asian (EAS) AF: 0.00404 AC: 160 AN: 39590

South Asian (SAS) AF: 0.164 AC: 14148 AN: 86032

European-Finnish (FIN) AF: 0.209 AC: 11167 AN: 53308

Middle Eastern (MID) AF: 0.283 AC: 1621 AN: 5732

European-Non Finnish (NFE) AF: 0.273 AC: 302840 AN: 1107412

Other (OTH) AF: 0.231 AC: 13897 AN: 60060

GnomAD4 genome AF: 0.213 AC: 32343 AN: 152016 Hom.: 3854 Cov.: 32 AF XY: 0.207 AC XY: 15406 AN XY: 74296

African (AFR) AF: 0.158 AC: 6537 AN: 41478

American (AMR) AF: 0.188 AC: 2865 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3468

East Asian (EAS) AF: 0.00522 AC: 27 AN: 5168

South Asian (SAS) AF: 0.149 AC: 719 AN: 4828

European-Finnish (FIN) AF: 0.209 AC: 2211 AN: 10566

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18355 AN: 67954

Other (OTH) AF: 0.225 AC: 475 AN: 2110

Alfa AF: 0.247 Hom.: 12181

Bravo AF: 0.210

TwinsUK AF: 0.275 AC: 1021

ALSPAC AF: 0.265 AC: 1021

ESP6500AA AF: 0.143 AC: 541

ESP6500EA AF: 0.267 AC: 2204

ExAC AF: 0.207 AC: 25050

Asia WGS AF: 0.0600 AC: 207 AN: 3478

EpiCase AF: 0.280

EpiControl AF: 0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.98
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.64	T
PhyloP100		0.23
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.29
Sift	Benign	0.38	T
Sift4G	Benign	0.37	T
Vest4		0.13
MPC		0.021
ClinPred		0.014	T
GERP RS		3.2
Mutation Taster		=96/4	polymorphism (auto)

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: rs1131498; hg19: chr1-169676486; COSMIC: COSV106354724; COSMIC: COSV106354724;