rs117392350
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004924.6(ACTN4):c.978G>A(p.Gln326=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,614,252 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0027 ( 11 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 64 hom. )
Consequence
ACTN4
NM_004924.6 synonymous
NM_004924.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.508
Genes affected
ACTN4 (HGNC:166): (actinin alpha 4) Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a nonmuscle, alpha actinin isoform which is concentrated in the cytoplasm, and thought to be involved in metastatic processes. Mutations in this gene have been associated with focal and segmental glomerulosclerosis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 19-38717151-G-A is Benign according to our data. Variant chr19-38717151-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.508 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00273 (416/152382) while in subpopulation AMR AF= 0.0237 (363/15302). AF 95% confidence interval is 0.0217. There are 11 homozygotes in gnomad4. There are 235 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 416 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN4 | NM_004924.6 | c.978G>A | p.Gln326= | synonymous_variant | 10/21 | ENST00000252699.7 | |
LOC107985291 | XR_001753937.2 | n.169+11037C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN4 | ENST00000252699.7 | c.978G>A | p.Gln326= | synonymous_variant | 10/21 | 1 | NM_004924.6 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00275 AC: 418AN: 152264Hom.: 11 Cov.: 33
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GnomAD3 exomes AF: 0.00581 AC: 1459AN: 251260Hom.: 48 AF XY: 0.00436 AC XY: 593AN XY: 135860
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GnomAD4 exome AF: 0.00142 AC: 2082AN: 1461870Hom.: 64 Cov.: 32 AF XY: 0.00123 AC XY: 898AN XY: 727242
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GnomAD4 genome ? AF: 0.00273 AC: 416AN: 152382Hom.: 11 Cov.: 33 AF XY: 0.00315 AC XY: 235AN XY: 74508
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 09, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 28, 2019 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Kidney disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Oct 01, 2019 | - - |
Focal segmental glomerulosclerosis 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at