NM_014639.4:c.3808C>G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_014639.4(SKIC3):c.3808C>G(p.Pro1270Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00043 in 1,613,796 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014639.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000276 AC: 42AN: 152024Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000622 AC: 156AN: 250826Hom.: 1 AF XY: 0.000730 AC XY: 99AN XY: 135698
GnomAD4 exome AF: 0.000447 AC: 653AN: 1461656Hom.: 3 Cov.: 32 AF XY: 0.000513 AC XY: 373AN XY: 727112
GnomAD4 genome AF: 0.000269 AC: 41AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74378
ClinVar
Submissions by phenotype
not provided Uncertain:4Benign:2
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In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23302111, 34426522, 29868001, 29527791, 21120949, 27035375, 37384835) -
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SKIC3: BP4, BS2 -
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Trichohepatoenteric syndrome 1 Uncertain:3
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TTC37 NM_014639.3 exon 37 p.Pro1270Ala (c.3808C>G): This variant has been reported in the literature in at least 2 individuals with trichohepatoenteric syndrome (Fabre 2011 PMID:21120949, Busoni 2017 PMID:28027214, Vely 2018 PMID:29868001). This variant is present in 0.02% (19/68016) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/5-95491031-G-C?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:430077). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at