chr16-21647417-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005849.4(IGSF6):c.143C>T(p.Thr48Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
IGSF6
NM_005849.4 missense
NM_005849.4 missense
Scores
3
6
9
Clinical Significance
Conservation
PhyloP100: 1.51
Genes affected
IGSF6 (HGNC:5953): (immunoglobulin superfamily member 6) Predicted to enable transmembrane signaling receptor activity. Predicted to be involved in cell surface receptor signaling pathway and immune response. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
METTL9 (HGNC:24586): (methyltransferase 9, His-X-His N1(pi)-histidine) Enables protein-L-histidine N-pros-methyltransferase activity. Predicted to be involved in methylation. Is active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17115533).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGSF6 | NM_005849.4 | c.143C>T | p.Thr48Ile | missense_variant | 2/6 | ENST00000268389.6 | |
METTL9 | NM_016025.5 | c.752-7810G>A | intron_variant | ENST00000358154.8 | |||
LOC124903663 | XR_007065025.1 | n.1267G>A | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGSF6 | ENST00000268389.6 | c.143C>T | p.Thr48Ile | missense_variant | 2/6 | 1 | NM_005849.4 | P1 | |
METTL9 | ENST00000358154.8 | c.752-7810G>A | intron_variant | 1 | NM_016025.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152086Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000128 AC: 32AN: 249734Hom.: 0 AF XY: 0.000126 AC XY: 17AN XY: 135194
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GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23AN XY: 727244
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74404
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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 submitter | clinical testing | Ambry Genetics | Dec 16, 2023 | The c.143C>T (p.T48I) alteration is located in exon 2 (coding exon 2) of the IGSF6 gene. This alteration results from a C to T substitution at nucleotide position 143, causing the threonine (T) at amino acid position 48 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Benign
D;T
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of glycosylation at T48 (P = 0.1054);Loss of glycosylation at T48 (P = 0.1054);
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at