chr5-66075145-A-T

Position:

• chr5-66075145-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 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).

• 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERBIN	NM_001253697.2	c.3878A>T	p.Tyr1293Phe	missense_variant	23/26	ENST00000284037.10	NP_001240626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERBIN	ENST00000284037.10	c.3878A>T	p.Tyr1293Phe	missense_variant	23/26	1	NM_001253697.2	ENSP00000284037	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

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;.;T;.;.;.;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.36	T;T;T;T;T;T;T
MetaSVM	Benign	-0.80	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.5	N;N;N;N;N;N;D
REVEL	Benign	0.24
Sift	Uncertain	0.011	D;D;T;D;D;D;D
Sift4G	Benign	0.19	T;T;D;T;T;T;D
Polyphen		1.0	D;D;D;P;.;.;.
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

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

LitVar

Other links and lift over

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