rs747480309

Variant names:

• chr1-8957233-C-A
• rs747480309
• NM_001215.4:c.356C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-8957233-C-A
• chr1-8957233-C-T

Variant summary

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

The NM_001215.4(CA6):​c.356C>A​(p.Ser119*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CA6 NM_001215.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 0 publications found

Genes affected

CA6 (HGNC:1380): (carbonic anhydrase 6) The protein encoded by this gene is one of several isozymes of carbonic anhydrase. This protein is found only in salivary glands and saliva and protein may play a role in the reversible hydratation of carbon dioxide though its function in saliva is unknown. [provided by RefSeq, Jul 2008]

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_001215.4. 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
	CA6	NM_001215.4	MANE Select	c.356C>A	p.Ser119*	stop_gained	Exon 3 of 8	NP_001206.2	P23280-1
	CA6	NM_001270500.2		c.356C>A	p.Ser119*	stop_gained	Exon 3 of 8	NP_001257429.1	P23280-2
	CA6	NM_001270501.2		c.176C>A	p.Ser59*	stop_gained	Exon 2 of 7	NP_001257430.1	P23280-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA6	ENST00000377443.7	TSL:1 MANE Select	c.356C>A	p.Ser119*	stop_gained	Exon 3 of 8	ENSP00000366662.2	P23280-1
	CA6	ENST00000377436.6	TSL:1	c.356C>A	p.Ser119*	stop_gained	Exon 3 of 8	ENSP00000366654.3	P23280-2
	CA6	ENST00000377442.3	TSL:1	c.176C>A	p.Ser59*	stop_gained	Exon 2 of 7	ENSP00000366661.2	P23280-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461836 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727212

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	28
DANN	Benign	0.97
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.085	N
PhyloP100		-0.23
Vest4		0.75
GERP RS		-3.5
Mutation Taster		=19/181	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs747480309; hg19: chr1-9017292;