NM_152558.5:c.324C>T

Variant names:

• chr7-2572256-C-T
• rs61736333
• NM_152558.5:c.324C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_152558.5(IQCE):​c.324C>T​(p.Gly108Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,614,100 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (68 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (50 hom.)
• Consequence: IQCE NM_152558.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.644
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 7-2572256-C-T is Benign according to our data. Variant chr7-2572256-C-T is described in ClinVar as Benign. ClinVar VariationId is 783483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.644 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152558.5. 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
	IQCE	NM_152558.5	MANE Select	c.324C>T	p.Gly108Gly	synonymous	Exon 5 of 22	NP_689771.3
	IQCE	NM_001287499.2		c.324C>T	p.Gly108Gly	synonymous	Exon 5 of 21	NP_001274428.1	A0A087WX45
	IQCE	NM_001287500.2		c.276C>T	p.Gly92Gly	synonymous	Exon 4 of 20	NP_001274429.1	A0A087WX19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCE	ENST00000402050.7	TSL:1 MANE Select	c.324C>T	p.Gly108Gly	synonymous	Exon 5 of 22	ENSP00000385597.2	Q6IPM2-1
	IQCE	ENST00000623361.3	TSL:1	c.129C>T	p.Gly43Gly	synonymous	Exon 3 of 20	ENSP00000485601.1	Q6IPM2-2
	IQCE	ENST00000325997.13	TSL:1	n.*101C>T		non_coding_transcript_exon	Exon 3 of 20	ENSP00000314011.10	X5D7Y5

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2328 AN: 152216 Hom.: 68 Cov.: 33

Gnomad AFR AF: 0.0531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00385 AC: 960 AN: 249494 AF XY: 0.00291

Gnomad AFR exome AF: 0.0543

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000883

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00152 AC: 2222 AN: 1461766 Hom.: 50 Cov.: 33 AF XY: 0.00133 AC XY: 966 AN XY: 727182

African (AFR) AF: 0.0532 AC: 1781 AN: 33480

American (AMR) AF: 0.00304 AC: 136 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53404

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0000675 AC: 75 AN: 1111910

Other (OTH) AF: 0.00344 AC: 208 AN: 60394

GnomAD4 genome AF: 0.0152 AC: 2323 AN: 152334 Hom.: 68 Cov.: 33 AF XY: 0.0145 AC XY: 1083 AN XY: 74502

African (AFR) AF: 0.0529 AC: 2199 AN: 41580

American (AMR) AF: 0.00582 AC: 89 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68028

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00722 Hom.: 12

Bravo AF: 0.0172

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.6
DANN	Benign	0.58
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs61736333; hg19: chr7-2611890;