NM_004056.6:c.576+5G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004056.6(CA8):​c.576+5G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CA8
NM_004056.6 splice_region, intron

Scores

2
Splicing: ADA: 0.6904
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.865
Variant links:
Genes affected
CA8 (HGNC:1382): (carbonic anhydrase 8) The protein encoded by this gene was initially named CA-related protein because of sequence similarity to other known carbonic anhydrase genes. However, the gene product lacks carbonic anhydrase activity (i.e., the reversible hydration of carbon dioxide). The gene product continues to carry a carbonic anhydrase designation based on clear sequence identity to other members of the carbonic anhydrase gene family. The absence of CA8 gene transcription in the cerebellum of the lurcher mutant in mice with a neurologic defect suggests an important role for this acatalytic form. Mutations in this gene are associated with cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CMARQ3). Polymorphisms in this gene are associated with osteoporosis, and overexpression of this gene in osteosarcoma cells suggests an oncogenic role. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.23).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CA8NM_004056.6 linkc.576+5G>T splice_region_variant, intron_variant Intron 5 of 8 ENST00000317995.5 NP_004047.3 P35219

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CA8ENST00000317995.5 linkc.576+5G>T splice_region_variant, intron_variant Intron 5 of 8 1 NM_004056.6 ENSP00000314407.4 P35219
CA8ENST00000524872.5 linkn.814+5G>T splice_region_variant, intron_variant Intron 5 of 7 1
CA8ENST00000528666.1 linkn.348+5G>T splice_region_variant, intron_variant Intron 3 of 4 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.18e-7
AC:
1
AN:
1393274
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
697296
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.23
CADD
Benign
16
DANN
Benign
0.91
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.2

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.69
dbscSNV1_RF
Benign
0.45
SpliceAI score (max)
0.080
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-61139427; API