rs146971634
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_018389.5(SLC35C1):c.598G>A(p.Val200Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000217 in 1,612,388 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_018389.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC35C1 | NM_018389.5 | c.598G>A | p.Val200Ile | missense_variant | 2/2 | ENST00000314134.4 | |
SLC35C1 | NM_001145265.2 | c.559G>A | p.Val187Ile | missense_variant | 3/3 | ||
SLC35C1 | NM_001145266.1 | c.559G>A | p.Val187Ile | missense_variant | 3/3 | ||
SLC35C1 | XM_011520202.3 | c.91G>A | p.Val31Ile | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC35C1 | ENST00000314134.4 | c.598G>A | p.Val200Ile | missense_variant | 2/2 | 1 | NM_018389.5 | P4 | |
SLC35C1 | ENST00000442528.2 | c.559G>A | p.Val187Ile | missense_variant | 3/3 | 1 | A1 | ||
SLC35C1 | ENST00000526817.2 | c.559G>A | p.Val187Ile | missense_variant | 3/3 | 2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00107 AC: 163AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000277 AC: 69AN: 248750Hom.: 1 AF XY: 0.000222 AC XY: 30AN XY: 134926
GnomAD4 exome AF: 0.000127 AC: 186AN: 1460036Hom.: 2 Cov.: 37 AF XY: 0.000105 AC XY: 76AN XY: 726456
GnomAD4 genome ? AF: 0.00108 AC: 164AN: 152352Hom.: 0 Cov.: 33 AF XY: 0.00110 AC XY: 82AN XY: 74496
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 09, 2021 | The c.598G>A (p.V200I) alteration is located in exon 2 (coding exon 2) of the SLC35C1 gene. This alteration results from a G to A substitution at nucleotide position 598, causing the valine (V) at amino acid position 200 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Leukocyte adhesion deficiency type II Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The SLC35C1 p.Val187Ile variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs146971634) and ClinVar (classified as likely benign). The variant was also identified in control databases in 107 of 280140 chromosomes (1 homozygous) at a frequency of 0.000382 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 94 of 24732 chromosomes (freq: 0.003801), Other in 3 of 7176 chromosomes (freq: 0.000418), Latino in 7 of 35384 chromosomes (freq: 0.000198), South Asian in 1 of 30614 chromosomes (freq: 0.000033) and European (non-Finnish) in 2 of 128374 chromosomes (freq: 0.000016), while the variant was not observed in the Ashkenazi Jewish, East Asian, and European (Finnish) populations. The p.Val187 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at