rs150167601
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP2BP4_StrongBS1_Supporting
The NM_003632.3(CNTNAP1):āc.3341A>Gā(p.Asp1114Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000077 in 1,610,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_003632.3 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 | UniProt |
---|---|---|---|---|---|---|---|
CNTNAP1 | NM_003632.3 | c.3341A>G | p.Asp1114Gly | missense_variant | 19/24 | ENST00000264638.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTNAP1 | ENST00000264638.9 | c.3341A>G | p.Asp1114Gly | missense_variant | 19/24 | 1 | NM_003632.3 | P1 | |
CNTNAP1 | ENST00000591662.1 | c.*1102A>G | 3_prime_UTR_variant, NMD_transcript_variant | 19/24 | 1 | ||||
ENST00000592440.1 | n.363+3235T>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000467 AC: 71AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000886 AC: 22AN: 248290Hom.: 0 AF XY: 0.0000447 AC XY: 6AN XY: 134320
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1458664Hom.: 0 Cov.: 31 AF XY: 0.0000331 AC XY: 24AN XY: 724998
GnomAD4 genome ? AF: 0.000466 AC: 71AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27AN XY: 74458
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 25, 2022 | BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 521338). This variant has not been reported in the literature in individuals affected with CNTNAP1-related conditions. This variant is present in population databases (rs150167601, gnomAD 0.1%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1114 of the CNTNAP1 protein (p.Asp1114Gly). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 30, 2022 | The c.3341A>G (p.D1114G) alteration is located in exon 19 (coding exon 19) of the CNTNAP1 gene. This alteration results from a A to G substitution at nucleotide position 3341, causing the aspartic acid (D) at amino acid position 1114 to be replaced by a glycine (G). 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