Genetic Variant EFCAB13:p.Val93Ile (chr17-47342006-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152347.5(EFCAB13):c.277G>A(p.Val93Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,595,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

EFCAB13
NM_152347.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.352

Publications

0 publications found

Variant links:

Genes affected

EFCAB13 (HGNC:26864): (EF-hand calcium binding domain 13)

EFCAB13 links:

ENSG00000259753 (HGNC:):

ENSG00000259753 links:

EFCAB13-DT (HGNC:55338): (EFCAB13 divergent transcript)

EFCAB13-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07409519).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152347.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EFCAB13	NM_152347.5	MANE Select	c.277G>A	p.Val93Ile	missense	Exon 6 of 25	NP_689560.3
EFCAB13	NM_001426585.1		c.277G>A	p.Val93Ile	missense	Exon 5 of 23	NP_001413514.1
EFCAB13	NM_001426586.1		c.277G>A	p.Val93Ile	missense	Exon 6 of 23	NP_001413515.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFCAB13	ENST00000331493.7	TSL:1 MANE Select	c.277G>A	p.Val93Ile	missense	Exon 6 of 25	ENSP00000332111.2	Q8IY85-1
ENSG00000259753	ENST00000560629.1	TSL:2	n.*266G>A		non_coding_transcript_exon	Exon 17 of 18	ENSP00000456711.2	H3BM21
ENSG00000259753	ENST00000560629.1	TSL:2	n.*266G>A		3_prime_UTR	Exon 17 of 18	ENSP00000456711.2	H3BM21

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000839

AC:

AN:

238492

AF XY:

0.00000775

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000145

AC:

AN:

1443556

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

718050

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32402

American (AMR)

AF:

0.00

AC:

AN:

41676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25862

East Asian (EAS)

AF:

0.00

AC:

AN:

39234

South Asian (SAS)

AF:

0.00

AC:

AN:

82338

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000163

AC:

AN:

1103284

Other (OTH)

AF:

0.0000502

AC:

AN:

59738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

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

AF:

0.0000263

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.00000824

AC:

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

Benign

0.094

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.0023

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.40

M_CAP

Benign

0.032

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.97

PhyloP100

0.35

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.14

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Benign

0.066

Polyphen

0.035

Vest4

0.11

MVP

0.030

MPC

0.13

ClinPred

0.077

GERP RS

0.65

Varity_R

0.11

gMVP

0.0075

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over