chr1-8949281-C-T

Variant names:

• chr1-8949281-C-T
• rs1156562439
• NM_001215.4:c.98C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001215.4(CA6):​c.98C>T​(p.Ala33Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,602,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CA6 NM_001215.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.65
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066785306).

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.98C>T	p.Ala33Val	missense	Exon 2 of 8	NP_001206.2	P23280-1
	CA6	NM_001270500.2		c.98C>T	p.Ala33Val	missense	Exon 2 of 8	NP_001257429.1	P23280-2
	CA6	NM_001270501.2		c.79+3316C>T		intron	N/A	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.98C>T	p.Ala33Val	missense	Exon 2 of 8	ENSP00000366662.2	P23280-1
	CA6	ENST00000377436.6	TSL:1	c.98C>T	p.Ala33Val	missense	Exon 2 of 8	ENSP00000366654.3	P23280-2
	CA6	ENST00000480186.7	TSL:2	c.98C>T	p.Ala33Val	missense	Exon 2 of 3	ENSP00000435280.1	Q8N4G4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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

GnomAD2 exomes AF: 0.00000416 AC: 1 AN: 240414 AF XY: 0.00000766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000317

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1450620 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 721626

African (AFR) AF: 0.00 AC: 0 AN: 32600

American (AMR) AF: 0.0000708 AC: 3 AN: 42360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25570

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39074

South Asian (SAS) AF: 0.00 AC: 0 AN: 84856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107256

Other (OTH) AF: 0.00 AC: 0 AN: 59884

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.000131 AC: 2 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.047
DANN	Benign	0.85
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-1.6
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.11
Sift	Benign	0.16	T
Sift4G	Benign	0.28	T
Polyphen		0.024	B
Vest4		0.18
MutPred		0.36		Loss of disorder (P = 0.0603)
MVP		0.32
MPC		0.15
ClinPred		0.084	T
GERP RS		-11
Varity_R		0.14
gMVP		0.34
Mutation Taster		=94/6	polymorphism

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: rs1156562439; hg19: chr1-9009340;