Variant 3-129004005-A-C 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_001377500.1(EFCC1):c.908A>C(p.Glu303Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000578 in 1,505,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E303G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

EFCC1
NM_001377500.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Variant links:

Genes affected

EFCC1 (HGNC:25692): (EF-hand and coiled-coil domain containing 1) Predicted to enable calcium ion binding activity. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

EFCC1 links:

CFAP92 (HGNC:):

CFAP92 links:

Genome browser will be placed here

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=0.24298456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFCC1	NM_001377500.1 linkuse as main transcript	c.908A>C	p.Glu303Ala	missense_variant	2/8	ENST00000683648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFCC1	ENST00000683648.1 linkuse as main transcript	c.908A>C	p.Glu303Ala	missense_variant	2/8		NM_001377500.1
EFCC1	ENST00000436022.2 linkuse as main transcript	c.908A>C	p.Glu303Ala	missense_variant	2/8	5		P1	Q9HA90-1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000110

AC:

AN:

100024

Hom.:

AF XY:

0.0000709

AC XY:

AN XY:

56416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000352

Gnomad SAS exome

AF:

0.000192

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000569

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000569

AC:

AN:

1353682

Hom.:

Cov.:

AF XY:

0.0000524

AC XY:

AN XY:

668074

show subpopulations

Gnomad4 AFR exome

AF:

0.0000716

Gnomad4 AMR exome

AF:

0.0000919

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000160

Gnomad4 SAS exome

AF:

0.0000645

Gnomad4 FIN exome

AF:

0.0000301

Gnomad4 NFE exome

AF:

0.0000553

Gnomad4 OTH exome

AF:

0.0000355

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000968

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000945

ExAC

AF:

0.000193

AC:

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

Nov 21, 2022

The c.908A>C (p.E303A) alteration is located in exon 2 (coding exon 2) of the EFCC1 gene. This alteration results from a A to C substitution at nucleotide position 908, causing the glutamic acid (E) at amino acid position 303 to be replaced by an alanine (A). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.59

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

Sift4G

Benign

0.16

Polyphen

1.0

Vest4

0.32

MutPred

0.23

Loss of solvent accessibility (P = 0.0703);

MVP

0.048

ClinPred

0.43

GERP RS

4.0

Varity_R

0.48

gMVP

0.38

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over