chr3-52818126-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002218.5(ITIH4):c.2222A>T(p.Gln741Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002218.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITIH4 | NM_002218.5 | c.2222A>T | p.Gln741Leu | missense_variant | 20/24 | ENST00000266041.9 | |
ITIH4 | NM_001166449.2 | c.2132A>T | p.Gln711Leu | missense_variant | 18/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITIH4 | ENST00000266041.9 | c.2222A>T | p.Gln741Leu | missense_variant | 20/24 | 1 | NM_002218.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000681 AC: 17AN: 249740Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135346
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461462Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 726978
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74334
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 10, 2022 | The c.2222A>T (p.Q741L) alteration is located in exon 20 (coding exon 20) of the ITIH4 gene. This alteration results from a A to T substitution at nucleotide position 2222, causing the glutamine (Q) at amino acid position 741 to be replaced by a leucine (L). 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