ENST00000325997.13:n.-2C>T

Variant names:

• chr7-2559055-G-T
• ENST00000470731.5:n.8G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000325997.13(IQCE):​n.-127G>T variant causes a upstream gene 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IQCE ENST00000325997.13 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 0 publications found

Genes affected

IQCE (HGNC:29171): (IQ motif containing E) Involved in limb morphogenesis. Predicted to be extrinsic component of membrane. Predicted to be part of plasma membrane protein complex. [provided by Alliance of Genome Resources, Apr 2022]

IQCE Gene-Disease associations (from GenCC):

• postaxial polydactyly type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• polydactyly, postaxial, type a7

  Inheritance: AR Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCE	NM_152558.5	c.-127G>T		5_prime_UTR_variant	Exon 1 of 22	ENST00000402050.7	NP_689771.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQCE	ENST00000402050.7	c.-127G>T		5_prime_UTR_variant	Exon 1 of 22	1	NM_152558.5	ENSP00000385597.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 315250 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 157550

African (AFR) AF: 0.00 AC: 0 AN: 7106

American (AMR) AF: 0.00 AC: 0 AN: 5892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7614

East Asian (EAS) AF: 0.00 AC: 0 AN: 19118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 234578

Other (OTH) AF: 0.00 AC: 0 AN: 16550

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Benign	0.77
PhyloP100		1.1
PromoterAI		0.55	Over-expression

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

Other links and lift over

hg19: chr7-2598689;