2-120074112-A-T

Variant names:

• chr2-120074112-A-T
• NM_020909.4:c.341A>T

Variant summary

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

The NM_020909.4(EPB41L5):​c.341A>T​(p.Tyr114Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Y114C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPB41L5 NM_020909.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.45

Genes affected

EPB41L5 (HGNC:19819): (erythrocyte membrane protein band 4.1 like 5) Predicted to enable cytoskeletal protein binding activity and protein domain specific binding activity. Predicted to be involved in actomyosin structure organization. Predicted to act upstream of or within several processes, including chordate embryonic development; embryonic foregut morphogenesis; and mesoderm morphogenesis. Located in cytosol; nucleoplasm; 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 rank	MANE	Protein	UniProt
EPB41L5	NM_020909.4	c.341A>T	p.Tyr114Phe	missense_variant	Exon 5 of 25	ENST00000263713.10	NP_065960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L5	ENST00000263713.10	c.341A>T	p.Tyr114Phe	missense_variant	Exon 5 of 25	1	NM_020909.4	ENSP00000263713.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.341A>T (p.Y114F) alteration is located in exon 5 (coding exon 4) of the EPB41L5 gene. This alteration results from a A to T substitution at nucleotide position 341, causing the tyrosine (Y) at amino acid position 114 to be replaced by a phenylalanine (F). 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	0.17
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T;.;.;.;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;.;D;D
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.57	D;D;D;D;D
MetaSVM	Uncertain	0.00090	D
MutationAssessor	Benign	1.3	L;L;L;L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D
REVEL	Pathogenic	0.74
Sift	Benign	0.052	T;T;T;T;T
Sift4G	Benign	0.10	T;T;T;T;T
Polyphen		1.0	D;D;P;P;.
Vest4		0.58
MutPred		0.64		Gain of MoRF binding (P = 0.075);Gain of MoRF binding (P = 0.075);Gain of MoRF binding (P = 0.075);Gain of MoRF binding (P = 0.075);Gain of MoRF binding (P = 0.075);
MVP		0.65
MPC		0.39
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.39
gMVP		0.37

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: chr2-120831688;