2-25131882-T-G

Position:

• chr2-25131882-T-G

Variant summary

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

The NM_014971.2(EFR3B):​c.1118T>G​(p.Met373Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EFR3B NM_014971.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.82

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFR3B	NM_014971.2	c.1118T>G	p.Met373Arg	missense_variant	10/23	ENST00000403714.8	NP_055786.1
EFR3B	NM_001319099.2	c.1013T>G	p.Met338Arg	missense_variant	10/23		NP_001306028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFR3B	ENST00000403714.8	c.1118T>G	p.Met373Arg	missense_variant	10/23	5	NM_014971.2	ENSP00000384081.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1390324 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 685466

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

Aug 26, 2024

The c.1118T>G (p.M373R) alteration is located in exon 10 (coding exon 10) of the EFR3B gene. This alteration results from a T to G substitution at nucleotide position 1118, causing the methionine (M) at amino acid position 373 to be replaced by an arginine (R). 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	0.14
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.062	.;T;.;.;.
Eigen	Benign	-0.060
Eigen_PC	Benign	0.068
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.38	T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.9	M;M;.;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.16	T;T;T;T;T
Sift4G	Benign	0.53	T;T;T;D;T
Polyphen		0.12	B;B;.;.;.
Vest4		0.47
MutPred		0.46		Gain of disorder (P = 0.0361);Gain of disorder (P = 0.0361);.;.;.;
MVP		0.18
ClinPred		0.61	D
GERP RS		4.1
Varity_R		0.43
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: 0

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: chr2-25354751;