2-25132986-C-T

Position:

• chr2-25132986-C-T

Variant summary

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

The NM_014971.2(EFR3B):​c.1231C>T​(p.His411Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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)
• Consequence: EFR3B NM_014971.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33

Genes affected

EFR3B (HGNC:29155): (EFR3 homolog B) Involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Located in actin cytoskeleton; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18006623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFR3B	NM_014971.2	c.1231C>T	p.His411Tyr	missense_variant	11/23	ENST00000403714.8	NP_055786.1
EFR3B	NM_001319099.2	c.1126C>T	p.His376Tyr	missense_variant	11/23		NP_001306028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFR3B	ENST00000403714.8	c.1231C>T	p.His411Tyr	missense_variant	11/23	5	NM_014971.2	ENSP00000384081.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Sep 26, 2024

The c.1231C>T (p.H411Y) alteration is located in exon 11 (coding exon 11) of the EFR3B gene. This alteration results from a C to T substitution at nucleotide position 1231, causing the histidine (H) at amino acid position 411 to be replaced by a tyrosine (Y). 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	0.080
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.037	.;T;.;.;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.74	T;T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.98	L;L;.;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Benign	0.076
Sift	Benign	0.60	T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;T
Polyphen		0.0010	B;B;.;.;.
Vest4		0.20
MutPred		0.42		Gain of phosphorylation at H411 (P = 0.0269);Gain of phosphorylation at H411 (P = 0.0269);.;.;.;
MVP		0.072
ClinPred		0.64	D
GERP RS		5.4
Varity_R		0.11
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-25355855;