9-34647712-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000155.4(GALT):c.377+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000155.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GALT | ENST00000378842.8 | c.377+7A>G | splice_region_variant, intron_variant | Intron 4 of 10 | 1 | NM_000155.4 | ENSP00000368119.4 | |||
ENSG00000258728 | ENST00000556278.1 | c.253-403A>G | intron_variant | Intron 2 of 7 | 5 | ENSP00000451792.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251416Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135898
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461862Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727226
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Galactosemia Uncertain:1
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not specified Benign:1
Variant summary: GALT c.377+7A>G alters a nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251416 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.377+7A>G has been observed in one newborn with elevated galactose level (Item_2002). The report does not provide unequivocal conclusions about association of the variant with Galactosemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 11919338). ClinVar contains an entry for this variant (Variation ID: 495677). Based on the evidence outlined above, the variant was classified as likely benign. -
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at