rs193921009

Variant names:

• chr5-66075145-A-T
• rs193921009
• NM_001253697.2:c.3878A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-66075145-A-T
• chr5-66075145-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001253697.2(ERBIN):​c.3878A>T​(p.Tyr1293Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y1293H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERBIN NM_001253697.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 8.49
• Publications: 0 publications found

Genes affected

ERBIN (HGNC:15842): (erbb2 interacting protein) This gene is a member of the leucine-rich repeat and PDZ domain (LAP) family. The encoded protein contains 17 leucine-rich repeats and one PDZ domain. It binds to the unphosphorylated form of the ERBB2 protein and regulates ERBB2 function and localization. It has also been shown to affect the Ras signaling pathway by disrupting Ras-Raf interaction. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ERBIN Gene-Disease associations (from GenCC):

• autosomal dominant combined immunodeficiency due to ERBIN deficiency

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3560475).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253697.2. 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
	ERBIN	NM_001253697.2	MANE Select	c.3878A>T	p.Tyr1293Phe	missense	Exon 23 of 26	NP_001240626.1	Q96RT1-1
	ERBIN	NM_001253699.2		c.3899A>T	p.Tyr1300Phe	missense	Exon 23 of 26	NP_001240628.1	Q96RT1-8
	ERBIN	NM_018695.4		c.3755A>T	p.Tyr1252Phe	missense	Exon 22 of 25	NP_061165.1	Q96RT1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERBIN	ENST00000284037.10	TSL:1 MANE Select	c.3878A>T	p.Tyr1293Phe	missense	Exon 23 of 26	ENSP00000284037.4	Q96RT1-1
	ERBIN	ENST00000506030.6	TSL:1	c.3899A>T	p.Tyr1300Phe	missense	Exon 23 of 26	ENSP00000426632.1	Q96RT1-8
	ERBIN	ENST00000380943.6	TSL:1	c.3755A>T	p.Tyr1252Phe	missense	Exon 22 of 25	ENSP00000370330.2	Q96RT1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.80	T
PhyloP100		8.5
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.24
Sift	Uncertain	0.011	D
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.63
MutPred		0.34		Loss of phosphorylation at Y1293 (P = 0.0123)
MVP		0.30
MPC		0.065
ClinPred		0.57	D
GERP RS		5.8
Varity_R		0.37
gMVP		0.32
Mutation Taster		=62/38	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

dbSNP: rs193921009; hg19: chr5-65370973; COSMIC: COSV52313112; COSMIC: COSV52313112;