1-1917008-G-T

Variant names:

• chr1-1917008-G-T
• rs201807862
• NM_138705.4:c.433G>T

Variant summary

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

The NM_138705.4(CALML6):​c.433G>T​(p.Glu145*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,644 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: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CALML6 NM_138705.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

Genes affected

CALML6 (HGNC:24193): (calmodulin like 6) Predicted to enable calcium ion binding activity and enzyme regulator activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALML6	NM_138705.4	c.433G>T	p.Glu145*	stop_gained	Exon 5 of 6	ENST00000307786.8	NP_619650.2
CALML6	NM_001330313.2	c.382G>T	p.Glu128*	stop_gained	Exon 4 of 5		NP_001317242.1
CALML6	XM_005244729.4	c.499G>T	p.Glu167*	stop_gained	Exon 5 of 6		XP_005244786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALML6	ENST00000307786.8	c.433G>T	p.Glu145*	stop_gained	Exon 5 of 6	1	NM_138705.4	ENSP00000304643.3
CALML6	ENST00000378604.3	c.382G>T	p.Glu128*	stop_gained	Exon 4 of 5	3		ENSP00000367867.3
CALML6	ENST00000462293.1	n.507G>T		non_coding_transcript_exon_variant	Exon 3 of 3	3
CALML6	ENST00000482402.1	n.1666G>T		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457644 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 724552

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	44
DANN	Uncertain	0.99
Eigen	Uncertain	0.25
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.65	D
Vest4		0.074
GERP RS		-0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.72		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.72		Position offset: 3

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

Publications

LitVar

Other links and lift over

dbSNP: rs201807862; hg19: chr1-1848447;