rs2269348

Variant names:

• chr12-56454697-T-A
• rs2269348
• ENST00000555551.1:n.317-942A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-56454697-T-A
• chr12-56454697-T-C
• chr12-56454697-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000555551.1(MIP):​n.317-942A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIP ENST00000555551.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 11 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIP	XM_011538354.2	c.76-942A>T		intron_variant	Intron 3 of 5		XP_011536656.1
MIP	NM_012064.4	c.-84A>T		upstream_gene_variant		ENST00000652304.1	NP_036196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285528	ENST00000648304.1	n.183-942A>T		intron_variant	Intron 1 of 3			ENSP00000497190.1
MIP	ENST00000652304.1	c.-84A>T		upstream_gene_variant			NM_012064.4	ENSP00000498622.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1425734 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 709124

African (AFR) AF: 0.00 AC: 0 AN: 32434

American (AMR) AF: 0.00 AC: 0 AN: 42550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24948

East Asian (EAS) AF: 0.00 AC: 0 AN: 39352

South Asian (SAS) AF: 0.00 AC: 0 AN: 83308

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4066

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1087700

Other (OTH) AF: 0.00 AC: 0 AN: 58830

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		0.051
PromoterAI		0.0070	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2269348; hg19: chr12-56848481;