1-1916501-G-C

Variant names:

• chr1-1916501-G-C
• NM_138705.4:c.139G>C

Variant summary

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

The NM_138705.4(CALML6):​c.139G>C​(p.Glu47Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,444,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 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. E47K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CALML6 NM_138705.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20702389).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALML6	NM_138705.4	c.139G>C	p.Glu47Gln	missense_variant	Exon 3 of 6	ENST00000307786.8	NP_619650.2
CALML6	NM_001330313.2	c.88G>C	p.Glu30Gln	missense_variant	Exon 2 of 5		NP_001317242.1
CALML6	XM_005244729.4	c.205G>C	p.Glu69Gln	missense_variant	Exon 3 of 6		XP_005244786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALML6	ENST00000307786.8	c.139G>C	p.Glu47Gln	missense_variant	Exon 3 of 6	1	NM_138705.4	ENSP00000304643.3
CALML6	ENST00000378604.3	c.88G>C	p.Glu30Gln	missense_variant	Exon 2 of 5	3		ENSP00000367867.3
CALML6	ENST00000482402.1	n.1236G>C		non_coding_transcript_exon_variant	Exon 1 of 3	2
CALML6	ENST00000462293.1	n.328-251G>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1444004 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 716944

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.70	N;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.54	N;N
REVEL	Benign	0.058
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.058	T;T
Polyphen		1.0	D;.
Vest4		0.28
MutPred		0.41		Loss of disorder (P = 0.0963);.;
MVP		0.66
MPC		0.32
ClinPred		0.52	D
GERP RS		0.28
Varity_R		0.094

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1847940;