rs372355067
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_014425.5(INVS):c.1038G>A(p.Ser346=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
INVS
NM_014425.5 synonymous
NM_014425.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.118
Genes affected
INVS (HGNC:17870): (inversin) This gene encodes a protein containing multiple ankyrin domains and two IQ calmodulin-binding domains. The encoded protein may function in renal tubular development and function, and in left-right axis determination. This protein interacts with nephrocystin and infers a connection between primary cilia function and left-right axis determination. A similar protein in mice interacts with calmodulin. Mutations in this gene have been associated with nephronophthisis type 2. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 9-100246747-G-A is Benign according to our data. Variant chr9-100246747-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 240908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.118 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INVS | NM_014425.5 | c.1038G>A | p.Ser346= | synonymous_variant | 8/17 | ENST00000262457.7 | |
INVS | NM_001318381.2 | c.750G>A | p.Ser250= | synonymous_variant | 9/18 | ||
INVS | NM_001318382.2 | c.60G>A | p.Ser20= | synonymous_variant | 8/17 | ||
INVS | NR_134606.2 | n.1236G>A | non_coding_transcript_exon_variant | 8/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INVS | ENST00000262457.7 | c.1038G>A | p.Ser346= | synonymous_variant | 8/17 | 1 | NM_014425.5 | A2 | |
INVS | ENST00000262456.6 | c.1038G>A | p.Ser346= | synonymous_variant | 8/18 | 5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152146Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251276Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135778
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461684Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727156
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GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74458
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
INVS-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 06, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Nephronophthisis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at