Genetic Variant EFCAB11:p.Asp144His (chr14-89797305-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_145231.4(EFCAB11):c.430G>C(p.Asp144His) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

EFCAB11
NM_145231.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46

Publications

0 publications found

Variant links:

Genes affected

EFCAB11 (HGNC:20357): (EF-hand calcium binding domain 11) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB11 links:

ENSG00000259053 (HGNC:):

ENSG00000259053 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.825

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145231.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFCAB11	NM_145231.4	MANE Select	c.430G>C	p.Asp144His	missense	Exon 6 of 6	NP_660274.1	Q9BUY7-1
EFCAB11	NM_001284269.2		c.358G>C	p.Asp120His	missense	Exon 6 of 6	NP_001271198.1	Q9BUY7-2
EFCAB11	NM_001284267.2		c.286G>C	p.Asp96His	missense	Exon 6 of 6	NP_001271196.1	Q9BUY7-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFCAB11	ENST00000316738.12	TSL:2 MANE Select	c.430G>C	p.Asp144His	missense	Exon 6 of 6	ENSP00000326267.7	Q9BUY7-1
EFCAB11	ENST00000555872.5	TSL:1	c.358G>C	p.Asp120His	missense	Exon 6 of 6	ENSP00000452320.1	Q9BUY7-2
EFCAB11	ENST00000905285.1		c.556G>C	p.Asp186His	missense	Exon 7 of 7	ENSP00000575344.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251110

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460982

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726820

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000671

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52938

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111712

Other (OTH)

AF:

0.0000166

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.94

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.82

MetaSVM

Uncertain

0.79

MutationAssessor

Pathogenic

4.1

PhyloP100

5.5

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.5

REVEL

Pathogenic

0.80

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.76

MutPred

0.55

Gain of catalytic residue at D144 (P = 0.0061)

MVP

0.93

MPC

0.39

ClinPred

1.0

GERP RS

6.0

Varity_R

0.70

gMVP

0.77

Mutation Taster

=47/53

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over