Genetic Variant SELL:p.Phe244Ser (chr1-169704603-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000655.5(SELL):c.731T>C(p.Phe244Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SELL
NM_000655.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.454

Variant links:

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]

SELL links:

C1orf112 (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

C1orf112 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0285317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELL	NM_000655.5 link	c.731T>C	p.Phe244Ser	missense_variant	Exon 5 of 9	ENST00000236147.6	NP_000646.3	P14151-1
SELL	NR_029467.2 link	n.700T>C		non_coding_transcript_exon_variant	Exon 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELL	ENST00000236147.6 link	c.731T>C	p.Phe244Ser	missense_variant	Exon 5 of 9	1	NM_000655.5	ENSP00000236147.5		P14151-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1428076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707018

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

32906

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

40416

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25510

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

38448

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

81598

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

51320

Gnomad4 NFE exome

AF:

0.00

AC:

AN:

1093018

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

59136

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 16, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.770T>C (p.F257S) alteration is located in exon 5 (coding exon 5) of the SELL gene. This alteration results from a T to C substitution at nucleotide position 770, causing the phenylalanine (F) at amino acid position 257 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.6

DANN

Benign

0.79

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.21

M_CAP

Benign

0.016

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

3.3

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.050

MVP

0.22

MPC

0.022

ClinPred

0.037

GERP RS

-5.5

Mutation Taster

=94/6

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over