3-129002029-G-C

Position:

• chr3-129002029-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001377500.1(EFCC1):​c.401G>C​(p.Arg134Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,392,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict 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. R134C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: EFCC1 NM_001377500.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.142

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]

CFAP92 (HGNC:29231): (cilia and flagella associated protein 92 (putative))

ACMG classification

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=0.23267221).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFCC1	NM_001377500.1	c.401G>C	p.Arg134Pro	missense_variant	1/8	ENST00000683648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFCC1	ENST00000683648.1	c.401G>C	p.Arg134Pro	missense_variant	1/8		NM_001377500.1
EFCC1	ENST00000436022.2	c.401G>C	p.Arg134Pro	missense_variant	1/8	5		P1
CFAP92	ENST00000510149.1	n.117+545C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000287 AC: 4 AN: 1392046 Hom.: 0 Cov.: 35 AF XY: 0.00000437 AC XY: 3 AN XY: 686416

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: 0.00000279

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.401G>C (p.R134P) alteration is located in exon 1 (coding exon 1) of the EFCC1 gene. This alteration results from a G to C substitution at nucleotide position 401, causing the arginine (R) at amino acid position 134 to be replaced by a proline (P). 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	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.78	T
Sift4G	Benign	0.24	T
Polyphen		0.97	D
Vest4		0.10
MutPred		0.29		Gain of loop (P = 0.0013);
MVP		0.048
ClinPred		0.86	D
GERP RS		3.4
Varity_R		0.25
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-128720872;