rs371405277

Variant names:

• chr20-36173938-C-A
• NM_012156.2:c.161C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-36173938-C-A
• chr20-36173938-C-G
• chr20-36173938-C-T

Variant summary

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

The NM_012156.2(EPB41L1):​c.161C>A​(p.Thr54Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. T54M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EPB41L1 NM_012156.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

Genes affected

EPB41L1 (HGNC:3378): (erythrocyte membrane protein band 4.1 like 1) Erythrocyte membrane protein band 4.1 (EPB41) is a multifunctional protein that mediates interactions between the erythrocyte cytoskeleton and the overlying plasma membrane. The encoded protein binds and stabilizes D2 and D3 dopamine receptors at the neuronal plasma membrane. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

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=0.07002476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L1	NM_012156.2	c.161C>A	p.Thr54Lys	missense_variant	Exon 2 of 22	ENST00000338074.7	NP_036288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L1	ENST00000338074.7	c.161C>A	p.Thr54Lys	missense_variant	Exon 2 of 22	1	NM_012156.2	ENSP00000337168.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461052 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726786

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: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.020	T;.;T;T;T;T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;.
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.070	T;T;T;T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	-0.34	.;.;.;.;.;N;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.6	N;.;N;N;D;N;N
REVEL	Benign	0.20
Sift	Benign	0.36	T;.;T;D;.;T;T
Sift4G	Benign	0.54	T;T;T;T;T;T;T
Polyphen		0.0, 0.039	.;.;B;.;.;B;.
Vest4		0.23, 0.17, 0.19
MutPred		0.23		Gain of ubiquitination at T54 (P = 0.0011);Gain of ubiquitination at T54 (P = 0.0011);Gain of ubiquitination at T54 (P = 0.0011);Gain of ubiquitination at T54 (P = 0.0011);Gain of ubiquitination at T54 (P = 0.0011);Gain of ubiquitination at T54 (P = 0.0011);Gain of ubiquitination at T54 (P = 0.0011);
MVP		0.51
MPC		0.89
ClinPred		0.21	T
GERP RS		5.8
Varity_R		0.15
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr20-34761860;