Variant 1-1916599-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_138705.4(CALML6):c.237G>T(p.Lys79Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000055 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CALML6
NM_138705.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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=0.14265436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CALML6	NM_138705.4 linkuse as main transcript	c.237G>T	p.Lys79Asn	missense_variant	3/6	ENST00000307786.8	NP_619650.2
CALML6	NM_001330313.2 linkuse as main transcript	c.186G>T	p.Lys62Asn	missense_variant	2/5		NP_001317242.1
CALML6	XM_005244729.4 linkuse as main transcript	c.303G>T	p.Lys101Asn	missense_variant	3/6		XP_005244786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CALML6	ENST00000307786.8 linkuse as main transcript	c.237G>T	p.Lys79Asn	missense_variant	3/6	1	NM_138705.4	ENSP00000304643	P2
CALML6	ENST00000378604.3 linkuse as main transcript	c.186G>T	p.Lys62Asn	missense_variant	2/5	3		ENSP00000367867	A2
CALML6	ENST00000482402.1 linkuse as main transcript	n.1334G>T		non_coding_transcript_exon_variant	1/3	2
CALML6	ENST00000462293.1 linkuse as main transcript	n.328-153G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245874

Hom.:

AF XY:

0.00

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000550

AC:

AN:

1455214

Hom.:

Cov.:

AF XY:

0.00000691

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000722

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000930

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.237G>T (p.K79N) alteration is located in exon 3 (coding exon 3) of the CALML6 gene. This alteration results from a G to T substitution at nucleotide position 237, causing the lysine (K) at amino acid position 79 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.015

T;.

Eigen

Benign

0.020

Eigen_PC

Benign

-0.010

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.077

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

0.61

N;N

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

0.25

GERP RS

3.0

Varity_R

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over