NM_020909.4:c.511C>T

Variant names:

• chr2-120076976-C-T
• rs201680783
• NM_020909.4:c.511C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020909.4(EPB41L5):​c.511C>T​(p.Leu171Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,441,872 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L171V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EPB41L5 NM_020909.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 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.511C>T	p.Leu171Phe	missense_variant	Exon 8 of 25	ENST00000263713.10	NP_065960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L5	ENST00000263713.10	c.511C>T	p.Leu171Phe	missense_variant	Exon 8 of 25	1	NM_020909.4	ENSP00000263713.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441872 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 716170

African (AFR) AF: 0.00 AC: 0 AN: 32774

American (AMR) AF: 0.00 AC: 0 AN: 41552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25482

East Asian (EAS) AF: 0.00 AC: 0 AN: 39212

South Asian (SAS) AF: 0.00 AC: 0 AN: 81924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102816

Other (OTH) AF: 0.00 AC: 0 AN: 59510

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;.;.;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D;.;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.73	D;D;D;D;D
MetaSVM	Uncertain	0.032	D
MutationAssessor	Benign	1.4	L;L;L;L;L
PhyloP100		3.9
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.8	D;D;D;D;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0080	D;D;D;D;D
Sift4G	Uncertain	0.0090	D;T;T;T;D
Polyphen		1.0	D;D;D;D;.
Vest4		0.73
MutPred		0.58		Loss of disorder (P = 0.1452);Loss of disorder (P = 0.1452);Loss of disorder (P = 0.1452);Loss of disorder (P = 0.1452);Loss of disorder (P = 0.1452);
MVP		0.69
MPC		0.46
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.54
gMVP		0.51
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201680783; hg19: chr2-120834552; COSMIC: COSV105822289;