rs111463603

Variant names:

• chr12-56450041-CAAAA-C
• rs111463603
• NM_012064.4:c.*1235_*1238delTTTT

Your query was ambiguous. Multiple possible variants found:

• chr12-56450041-CAAAA-C
• chr12-56450041-CAAAA-CAA
• chr12-56450041-CAAAA-CAAA
• chr12-56450041-CAAAA-CAAAAA
• chr12-56450041-CAAAA-CAAAAAA
• chr12-56450041-CAAAA-CAAAAAAA

Variant summary

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

The NM_012064.4(MIP):​c.*1235_*1238delTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000068 (0 hom., cov: 0)
• Consequence: MIP NM_012064.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• cataract 15 multiple types

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• cerulean cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset lamellar cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset nuclear cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset posterior polar cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset sutural cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285528 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012064.4. 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
	MIP	NM_012064.4	MANE Select	c.*1235_*1238delTTTT		3_prime_UTR	Exon 4 of 4	NP_036196.1	P30301

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIP	ENST00000652304.1	MANE Select	c.*1235_*1238delTTTT		3_prime_UTR	Exon 4 of 4	ENSP00000498622.1	P30301
	ENSG00000285528	ENST00000648304.1		n.*1651_*1654delTTTT		non_coding_transcript_exon	Exon 4 of 4	ENSP00000497190.1	A0A3B3IS89
	ENSG00000285528	ENST00000648304.1		n.*1651_*1654delTTTT		3_prime_UTR	Exon 4 of 4	ENSP00000497190.1	A0A3B3IS89

Frequencies

GnomAD3 genomes AF: 0.00000682 AC: 1 AN: 146534 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000682 AC: 1 AN: 146534 Hom.: 0 Cov.: 0 AF XY: 0.0000141 AC XY: 1 AN XY: 71044

African (AFR) AF: 0.00 AC: 0 AN: 39902

American (AMR) AF: 0.00 AC: 0 AN: 14704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5088

South Asian (SAS) AF: 0.000214 AC: 1 AN: 4664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66628

Other (OTH) AF: 0.00 AC: 0 AN: 2014

Alfa AF: 0.00 Hom.: 2029

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.67

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

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

Other links and lift over

dbSNP: rs111463603; hg19: chr12-56843825;