rs57677078

Variant names:

• chr8-60189993-CAAAAA-C
• rs57677078
• NM_004056.6:c.*36-13_*36-9delTTTTT

Your query was ambiguous. Multiple possible variants found:

• chr8-60189993-CAAAAA-C
• chr8-60189993-CAAAAA-CA
• chr8-60189993-CAAAAA-CAA
• chr8-60189993-CAAAAA-CAAA
• chr8-60189993-CAAAAA-CAAAA
• chr8-60189993-CAAAAA-CAAAAAA
• chr8-60189993-CAAAAA-CAAAAAAA
• chr8-60189993-CAAAAA-CAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004056.6(CA8):​c.*36-13_*36-9delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 109,306 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., cov: 26)
  • Failed GnomAD Quality Control
• Consequence: CA8 NM_004056.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495
• Publications: 0 publications found

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]

CA8 Gene-Disease associations (from GenCC):

• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• cerebellar ataxia

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• cerebellar ataxia, intellectual disability, and dysequilibrium

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004056.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA8	NM_004056.6	MANE Select	c.*36-13_*36-9delTTTTT		intron	N/A	NP_004047.3
	CA8	NM_001321839.2		c.*36-13_*36-9delTTTTT		intron	N/A	NP_001308768.1
	CA8	NR_135821.2		n.1212-13_1212-9delTTTTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA8	ENST00000317995.5	TSL:1 MANE Select	c.*36-13_*36-9delTTTTT		intron	N/A	ENSP00000314407.4	P35219
	CA8	ENST00000943617.1		c.*36-16_*36-12delTTTTT		intron	N/A	ENSP00000613676.1
	CA8	ENST00000943619.1		c.*36-13_*36-9delTTTTT		intron	N/A	ENSP00000613678.1

Frequencies

GnomAD3 genomes AF: 0.0000183 AC: 2 AN: 109306 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000183 AC: 2 AN: 109306 Hom.: 0 Cov.: 26 AF XY: 0.0000191 AC XY: 1 AN XY: 52246

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000288 AC: 1 AN: 34738

American (AMR) AF: 0.000103 AC: 1 AN: 9674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2552

East Asian (EAS) AF: 0.00 AC: 0 AN: 3594

South Asian (SAS) AF: 0.00 AC: 0 AN: 3458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 47192

Other (OTH) AF: 0.00 AC: 0 AN: 1454

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000812204), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

Splicing

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

Other links and lift over

dbSNP: rs57677078; hg19: chr8-61102552;