rs142116829
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_006172.4(NPPA):āc.83T>Cā(p.Met28Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000372 in 1,614,112 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_006172.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPPA | NM_006172.4 | c.83T>C | p.Met28Thr | missense_variant | 1/3 | ENST00000376480.7 | |
NPPA-AS1 | NR_037806.1 | n.1648A>G | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPPA | ENST00000376480.7 | c.83T>C | p.Met28Thr | missense_variant | 1/3 | 1 | NM_006172.4 | P1 | |
CLCN6 | ENST00000446542.5 | n.950A>G | non_coding_transcript_exon_variant | 4/4 | 1 | ||||
NPPA | ENST00000376476.1 | c.-27-163T>C | intron_variant | 3 | |||||
CLCN6 | ENST00000400892.3 | c.*1987A>G | 3_prime_UTR_variant, NMD_transcript_variant | 27/27 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00198 AC: 301AN: 152102Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.000549 AC: 138AN: 251496Hom.: 1 AF XY: 0.000478 AC XY: 65AN XY: 135922
GnomAD4 exome AF: 0.000205 AC: 300AN: 1461892Hom.: 2 Cov.: 33 AF XY: 0.000188 AC XY: 137AN XY: 727246
GnomAD4 genome ? AF: 0.00198 AC: 301AN: 152220Hom.: 3 Cov.: 32 AF XY: 0.00188 AC XY: 140AN XY: 74432
ClinVar
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 15, 2018 | Variant summary: The NPPA c.83T>C (p.Met28Thr) variant involves the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 181/277216 control chromosomes (1 homozygote) from all ethnicities, but was predominantly observed in the African subpopulation at a frequency of 0.006452 (155/24022; 1 homozygote). This frequency is about 645 times the estimated maximal expected allele frequency of a pathogenic NPPA variant (0.00001), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. One clinical diagnostic laboratory classified this variant as likely benign. In addition, an internal LCA sample carries this variant along with a pathogenic KCNQ1 variant (c.727C>T, p.R243C). The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. - |
Atrial fibrillation, familial, 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at