chr12-56453080-T-TAGTGGAATGTTCCC

Position:

• chr12-56453080-T-TAGTGGAATGTTCCC

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_012064.4(MIP):​c.597_598insGGGAACATTCCACT​(p.Asn200fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIP NM_012064.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.18

Genes affected

MIP (HGNC:7103): (major intrinsic protein of lens fiber) Major intrinsic protein is a member of the water-transporting aquaporins as well as the original member of the MIP family of channel proteins. The function of the fiber cell membrane protein encoded by this gene is undetermined, yet this protein is speculated to play a role in intracellular communication. The MIP protein is expressed in the ocular lens and is required for correct lens function. This gene has been mapped among aquaporins AQP2, AQP5, and AQP6, in a potential gene cluster at 12q13. [provided by RefSeq, Jul 2008]

MIP (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.246 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-56453080-T-TAGTGGAATGTTCCC is Pathogenic according to our data. Variant chr12-56453080-T-TAGTGGAATGTTCCC is described in ClinVar as [Pathogenic]. Clinvar id is 217345.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIP	NM_012064.4	c.597_598insGGGAACATTCCACT	p.Asn200fs	frameshift_variant	3/4	ENST00000652304.1	NP_036196.1
MIP	XM_011538354.2	c.312_313insGGGAACATTCCACT	p.Asn105fs	frameshift_variant	5/6		XP_011536656.1
MIP	XM_017019306.2	c.240_241insGGGAACATTCCACT	p.Asn81fs	frameshift_variant	3/4		XP_016874795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIP	ENST00000652304.1	c.597_598insGGGAACATTCCACT	p.Asn200fs	frameshift_variant	3/4		NM_012064.4	ENSP00000498622.1
ENSG00000285528	ENST00000648304.1	n.*221_*222insGGGAACATTCCACT		non_coding_transcript_exon_variant	3/4			ENSP00000497190.1
ENSG00000285528	ENST00000648304.1	n.*221_*222insGGGAACATTCCACT		3_prime_UTR_variant	3/4			ENSP00000497190.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Developmental cataract Pathogenic:1

Pathogenic, no assertion criteria provided

research

Eye Genetics Research Group, Children's Medical Research Institute

Jan 09, 2015

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs864309696; hg19: chr12-56846864;