rs11793196
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBA1
The NM_012144.4(DNAI1):c.1003G>A(p.Val335Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,613,248 control chromosomes in the GnomAD database, including 20,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V335F) has been classified as Likely pathogenic.
Frequency
Consequence
NM_012144.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAI1 | NM_012144.4 | c.1003G>A | p.Val335Ile | missense_variant | 11/20 | ENST00000242317.9 | |
DNAI1 | NM_001281428.2 | c.1015G>A | p.Val339Ile | missense_variant | 11/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAI1 | ENST00000242317.9 | c.1003G>A | p.Val335Ile | missense_variant | 11/20 | 1 | NM_012144.4 | ||
DNAI1 | ENST00000614641.4 | c.1015G>A | p.Val339Ile | missense_variant | 11/20 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.195 AC: 29683AN: 152068Hom.: 3445 Cov.: 32
GnomAD3 exomes AF: 0.153 AC: 38388AN: 251262Hom.: 3459 AF XY: 0.149 AC XY: 20211AN XY: 135800
GnomAD4 exome AF: 0.149 AC: 218086AN: 1461062Hom.: 17546 Cov.: 32 AF XY: 0.149 AC XY: 108235AN XY: 726868
GnomAD4 genome AF: 0.195 AC: 29714AN: 152186Hom.: 3449 Cov.: 32 AF XY: 0.192 AC XY: 14274AN XY: 74414
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Benign:4
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 11, 2014 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Val335Ile in exon 11 of DNAI1: This variant is not expected to have clinical sig nificance because it has been identified in 32.2% (1420/4406) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs11793196). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Kartagener syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 27, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at