1-169691801-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000655.5(SELL):ā€‹c.1102A>Gā€‹(p.Met368Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000305 in 1,375,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 32)
Exomes š‘“: 0.000027 ( 0 hom. )

Consequence

SELL
NM_000655.5 missense, splice_region

Scores

17
Splicing: ADA: 0.00006027
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.782
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]
C1orf112 (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.030453593).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SELLNM_000655.5 linkuse as main transcriptc.1102A>G p.Met368Val missense_variant, splice_region_variant 9/9 ENST00000236147.6 NP_000646.3 P14151-1
SELLNR_029467.2 linkuse as main transcriptn.1071A>G splice_region_variant, non_coding_transcript_exon_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SELLENST00000236147.6 linkuse as main transcriptc.1102A>G p.Met368Val missense_variant, splice_region_variant 9/91 NM_000655.5 ENSP00000236147.5 P14151-1
SELLENST00000650983.1 linkuse as main transcriptc.1141A>G p.Met381Val missense_variant, splice_region_variant 9/9 ENSP00000498227.1 P14151-2
SELLENST00000497295.1 linkuse as main transcriptc.94A>G p.Met32Val missense_variant, splice_region_variant 3/35 ENSP00000498707.1 A0A494C0S7
C1orf112ENST00000498289.5 linkuse as main transcriptn.851+7869T>C intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000522
AC:
7
AN:
134142
Hom.:
0
AF XY:
0.0000408
AC XY:
3
AN XY:
73536
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000988
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000270
AC:
33
AN:
1223032
Hom.:
0
Cov.:
24
AF XY:
0.0000383
AC XY:
23
AN XY:
599932
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000325
Gnomad4 OTH exome
AF:
0.0000204
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000154
Hom.:
0
Bravo
AF:
0.0000982
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000246
AC:
2
ExAC
AF:
0.0000415
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 10, 2024The c.1141A>G (p.M381V) alteration is located in exon 9 (coding exon 9) of the SELL gene. This alteration results from a A to G substitution at nucleotide position 1141, causing the methionine (M) at amino acid position 381 to be replaced by a valine (V). 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
0.065
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
1.8
DANN
Benign
0.84
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.072
N
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.030
T
MetaSVM
Benign
-0.92
T
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.33
N
REVEL
Benign
0.012
Sift
Benign
0.28
T
Sift4G
Benign
0.16
T
Vest4
0.11
MVP
0.16
MPC
0.019
ClinPred
0.029
T
GERP RS
-1.6

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000060
dbscSNV1_RF
Benign
0.018
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs367825789; hg19: chr1-169660942; API