5-141150948-GTT-ATC

Variant names:

• chr5-141150948-GTT-ATC
• NM_018939.4:c.691_693delGTTinsATC
• PCDHB6 p.Val231Ile

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_018939.4(PCDHB6):​c.691_693delGTTinsATC​(p.Val231Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCDHB6 NM_018939.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02
• Publications: 0 publications found

Genes affected

PCDHB6 (HGNC:8691): (protocadherin beta 6) This gene is a member of the protocadherin beta gene cluster, one of three related gene clusters tandemly linked on chromosome five. The gene clusters demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. Unlike the alpha and gamma clusters, the transcripts from these genes do not share common 3' exons. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell neural connections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

PCDHB@ (HGNC:8679):

ENSG00000280029 (HGNC:):

ENSG00000272154 (HGNC:59172):

ACMG classification

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

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018939.4. 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
	PCDHB6	NM_018939.4	MANE Select	c.691_693delGTTinsATC	p.Val231Ile	missense	N/A	NP_061762.2	Q9Y5E3
	PCDHB6	NM_001303145.2		c.283_285delGTTinsATC	p.Val95Ile	missense	N/A	NP_001290074.1	A0A096LNH7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDHB6	ENST00000231136.4	TSL:6 MANE Select	c.691_693delGTTinsATC	p.Val231Ile	missense	N/A	ENSP00000231136.1	Q9Y5E3
	PCDHB6	ENST00000622991.1	TSL:2	c.283_285delGTTinsATC	p.Val95Ile	missense	N/A	ENSP00000485034.1	A0A096LNH7
	ENSG00000280029	ENST00000624192.1	TSL:5	n.73-13767_73-13765delAACinsGAT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-140530529;