12-56450041-C-CA

Position:

• chr12-56450041-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012064.4(MIP):​c.*1238_*1239insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (60106 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: MIP NM_012064.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.669

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-56450041-C-CA is Benign according to our data. Variant chr12-56450041-C-CA is described in ClinVar as [Benign]. Clinvar id is 309863.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIP	NM_012064.4	c.*1238_*1239insT		3_prime_UTR_variant	4/4	ENST00000652304.1	NP_036196.1
MIP	XM_011538354.2	c.*1238_*1239insT		3_prime_UTR_variant	6/6		XP_011536656.1
MIP	XM_017019306.2	c.*1238_*1239insT		3_prime_UTR_variant	4/4		XP_016874795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIP	ENST00000652304.1	c.*1238_*1239insT		3_prime_UTR_variant	4/4		NM_012064.4	ENSP00000498622	P1

Frequencies

GnomAD3 genomes AF: 0.900 AC: 131927 AN: 146522 Hom.: 60101 Cov.: 0

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.994

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.955

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.926

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.900 AC: 131965 AN: 146596 Hom.: 60106 Cov.: 0 AF XY: 0.902 AC XY: 64159 AN XY: 71124

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.955

Gnomad4 EAS AF: 0.989

Gnomad4 SAS AF: 0.988

Gnomad4 FIN AF: 0.949

Gnomad4 NFE AF: 0.968

Gnomad4 OTH AF: 0.923

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cataract Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs111463603; hg19: chr12-56843825;