19-51491682-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_053003.4(SIGLEC12):c.1747G>T(p.Ala583Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,613,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_053003.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SIGLEC12 | NM_053003.4 | c.1747G>T | p.Ala583Ser | missense_variant | 8/8 | ENST00000291707.8 | NP_443729.1 | |
SIGLEC12 | NM_033329.2 | c.1393G>T | p.Ala465Ser | missense_variant | 7/7 | NP_201586.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SIGLEC12 | ENST00000291707.8 | c.1747G>T | p.Ala583Ser | missense_variant | 8/8 | 1 | NM_053003.4 | ENSP00000291707.3 | ||
SIGLEC12 | ENST00000596742.1 | n.*962G>T | non_coding_transcript_exon_variant | 8/8 | 1 | ENSP00000469791.1 | ||||
SIGLEC12 | ENST00000596742.1 | n.*962G>T | 3_prime_UTR_variant | 8/8 | 1 | ENSP00000469791.1 | ||||
SIGLEC12 | ENST00000598614.1 | c.1393G>T | p.Ala465Ser | missense_variant | 7/7 | 5 | ENSP00000472873.1 |
Frequencies
GnomAD3 genomes AF: 0.0000528 AC: 8AN: 151574Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251404Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135874
GnomAD4 exome AF: 0.000190 AC: 278AN: 1461798Hom.: 0 Cov.: 31 AF XY: 0.000183 AC XY: 133AN XY: 727200
GnomAD4 genome AF: 0.0000528 AC: 8AN: 151574Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2AN XY: 74032
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 01, 2024 | The c.1747G>T (p.A583S) alteration is located in exon 8 (coding exon 8) of the SIGLEC12 gene. This alteration results from a G to T substitution at nucleotide position 1747, causing the alanine (A) at amino acid position 583 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at