Variant 3-129003908-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_001377500.1(EFCC1):c.811G>T(p.Ala271Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000333 in 1,199,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

EFCC1
NM_001377500.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

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:29231): (cilia and flagella associated protein 92 (putative))

CFAP92 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=0.10710147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFCC1	NM_001377500.1 linkuse as main transcript	c.811G>T	p.Ala271Ser	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.811G>T	p.Ala271Ser	missense_variant	2/8		NM_001377500.1
EFCC1	ENST00000436022.2 linkuse as main transcript	c.811G>T	p.Ala271Ser	missense_variant	2/8	5		P1	Q9HA90-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000482

AC:

AN:

20736

Hom.:

AF XY:

0.0000777

AC XY:

AN XY:

12876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000301

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000333

AC:

AN:

1199632

Hom.:

Cov.:

AF XY:

0.00000681

AC XY:

AN XY:

587172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000823

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000382

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000202

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 24, 2023

The c.811G>T (p.A271S) alteration is located in exon 2 (coding exon 2) of the EFCC1 gene. This alteration results from a G to T substitution at nucleotide position 811, causing the alanine (A) at amino acid position 271 to be replaced by a serine (S). 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

0.16

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0032

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.58

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.51

M_CAP

Benign

0.031

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

MutationTaster

Benign

0.99

D;N

PrimateAI

Pathogenic

0.85

Sift4G

Benign

0.76

Polyphen

0.11

Vest4

0.045

MutPred

0.31

Gain of relative solvent accessibility (P = 0.0023);

MVP

0.014

ClinPred

0.062

GERP RS

1.5

Varity_R

0.074

gMVP

0.072

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