Variant 5-112168749-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022140.5(EPB41L4A):c.1922C>A(p.Thr641Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,966 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000027 ( 0 hom. )

Consequence

EPB41L4A
NM_022140.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Variant links:

Genes affected

EPB41L4A (HGNC:13278): (erythrocyte membrane protein band 4.1 like 4A) The protein encoded by this gene is a member of the band 4.1 protein superfamily. Members of this superfamily are thought to play an important role in regulating interactions between the cytoskeleton and plasma membrane, and contain an amino terminal conserved domain that binds glycophorin C. This gene product is thought to be involved in the beta-catenin signaling pathway. [provided by RefSeq, Dec 2016]

EPB41L4A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.17759112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L4A	NM_022140.5 linkuse as main transcript	c.1922C>A	p.Thr641Lys	missense_variant	22/23	ENST00000261486.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EPB41L4A	ENST00000261486.6 linkuse as main transcript	c.1922C>A	p.Thr641Lys	missense_variant	22/23	1	NM_022140.5	P1
EPB41L4A	ENST00000507810.5 linkuse as main transcript	n.942C>A		non_coding_transcript_exon_variant	11/14	2
EPB41L4A	ENST00000509342.6 linkuse as main transcript	n.370C>A		non_coding_transcript_exon_variant	5/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249480

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460966

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

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.:

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2021

The c.1922C>A (p.T641K) alteration is located in exon 22 (coding exon 22) of the EPB41L4A gene. This alteration results from a C to A substitution at nucleotide position 1922, causing the threonine (T) at amino acid position 641 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.21

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

0.081

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.69

T;.

M_CAP

Benign

0.037

MetaRNN

Benign

0.18

T;T

MetaSVM

Uncertain

0.033

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

0.92

PrimateAI

Benign

0.42

Sift4G

Benign

0.40

T;T

Polyphen

0.18

B;B

Vest4

0.33

MutPred

0.32

Gain of ubiquitination at T641 (P = 0.0037);Gain of ubiquitination at T641 (P = 0.0037);

MVP

0.87

MPC

0.059

ClinPred

0.42

GERP RS

5.7

Varity_R

0.088

gMVP

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over