dbSNP rs1375806965: CALML6:p.Lys79Asn (chr1-1916599-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138705.4(CALML6):c.237G>C(p.Lys79Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CALML6
NM_138705.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.106

Variant links:

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]

CALML6 links:

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ACMG classification

Classification made for transcript

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=0.13949424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALML6	NM_138705.4 link	c.237G>C	p.Lys79Asn	missense_variant	Exon 3 of 6	ENST00000307786.8	NP_619650.2	Q8TD86
CALML6	NM_001330313.2 link	c.186G>C	p.Lys62Asn	missense_variant	Exon 2 of 5		NP_001317242.1	B1AKR1
CALML6	XM_005244729.4 link	c.303G>C	p.Lys101Asn	missense_variant	Exon 3 of 6		XP_005244786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CALML6	ENST00000307786.8 link	c.237G>C	p.Lys79Asn	missense_variant	Exon 3 of 6	1	NM_138705.4	ENSP00000304643.3	Q8TD86
CALML6	ENST00000378604.3 link	c.186G>C	p.Lys62Asn	missense_variant	Exon 2 of 5	3		ENSP00000367867.3	B1AKR1
CALML6	ENST00000482402.1 link	n.1334G>C		non_coding_transcript_exon_variant	Exon 1 of 3	2
CALML6	ENST00000462293.1 link	n.328-153G>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245874

Hom.:

AF XY:

0.00000752

AC XY:

AN XY:

133066

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455214

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723130

show subpopulations

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.015

T;.

Eigen

Benign

0.020

Eigen_PC

Benign

-0.010

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.077

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.37

PROVEAN

Benign

2.9

N;N

REVEL

Uncertain

0.31

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.99

D;.

Vest4

0.22

MutPred

0.34

Loss of ubiquitination at K79 (P = 0.0148);.;

MVP

0.85

MPC

0.27

ClinPred

0.20

GERP RS

3.0

Varity_R

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over