chr1-8970867-G-C

Variant names:

• chr1-8970867-G-C
• rs1261100664
• NM_001215.4:c.730G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001215.4(CA6):​c.730G>C​(p.Val244Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,450,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V244F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CA6 NM_001215.4 missense, splice_region
• Scores: Splicing: ADA: 0.03101
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

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]

ENSG00000290109 (HGNC:):

ACMG classification

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 (MetaRNN=0.13093576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA6	NM_001215.4	c.730G>C	p.Val244Leu	missense_variant, splice_region_variant	Exon 7 of 8	ENST00000377443.7	NP_001206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA6	ENST00000377443.7	c.730G>C	p.Val244Leu	missense_variant, splice_region_variant	Exon 7 of 8	1	NM_001215.4	ENSP00000366662.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1450164 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 722224

Gnomad4 AFR exome AF: 0.0000301

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: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.4
DANN	Benign	0.27
DEOGEN2	Benign	0.038	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.84	T;T;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.36	N;N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.70	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.74	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.22	B;.;.
Vest4		0.088
MutPred		0.64		Loss of methylation at K246 (P = 0.0798);Loss of methylation at K246 (P = 0.0798);.;
MVP		0.36
MPC		0.20
ClinPred		0.16	T
GERP RS		-6.0
Varity_R		0.21
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.031
dbscSNV1_RF	Benign	0.34
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.28		Position offset: -39

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

Publications

LitVar

Other links and lift over

dbSNP: rs1261100664; hg19: chr1-9030926;