9-109185572-A-T

Variant names:

• chr9-109185572-A-T
• NM_019114.5:c.2335T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019114.5(EPB41L4B):​c.2335T>A​(p.Ser779Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPB41L4B NM_019114.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69
• Publications: 0 publications found

Genes affected

EPB41L4B (HGNC:19818): (erythrocyte membrane protein band 4.1 like 4B) Predicted to be a structural constituent of cytoskeleton. Involved in several processes, including positive regulation of cell adhesion; positive regulation of keratinocyte migration; and wound healing. Acts upstream of or within actomyosin structure organization. Located in apical part of cell; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1597698).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019114.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L4B	NM_019114.5	MANE Select	c.2335T>A	p.Ser779Thr	missense	Exon 23 of 26	NP_061987.3
	EPB41L4B	NM_001385623.1		c.2311-2775T>A		intron	N/A	NP_001372552.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L4B	ENST00000374566.8	TSL:1 MANE Select	c.2335T>A	p.Ser779Thr	missense	Exon 23 of 26	ENSP00000363694.3	Q9H329-1
	EPB41L4B	ENST00000952218.1		c.2449T>A	p.Ser817Thr	missense	Exon 24 of 27	ENSP00000622277.1
	EPB41L4B	ENST00000952215.1		c.2344T>A	p.Ser782Thr	missense	Exon 23 of 26	ENSP00000622274.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.037
Eigen_PC	Benign	0.076
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.29
Sift	Uncertain	0.024	D
Sift4G	Benign	0.80	T
Polyphen		0.43	B
Vest4		0.40
MutPred		0.14		Loss of glycosylation at S779 (P = 0.0505)
MVP		0.55
MPC		0.23
ClinPred		0.47	T
GERP RS		4.2
Varity_R		0.082
gMVP		0.24
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chr9-111947852;