Genetic Variant INTU:p.Glu355Gln (chr4-127669126-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015693.4(INTU):c.1063G>C(p.Glu355Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,386,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 0.0000014 ( 0 hom. )

Consequence

INTU
NM_015693.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.03

Publications

0 publications found

Variant links:

Genes affected

INTU (HGNC:29239): (inturned planar cell polarity protein) Involved in embryonic digit morphogenesis; roof of mouth development; and tongue morphogenesis. Located in ciliary basal body and motile cilium. Implicated in asphyxiating thoracic dystrophy and orofaciodigital syndrome XVII. [provided by Alliance of Genome Resources, Apr 2022]

INTU Gene-Disease associations (from GenCC):

INTU-related skeletal ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
orofaciodigital syndrome 17
Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
short-rib thoracic dysplasia 20 with polydactyly
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

INTU links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2707737).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015693.4. 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
	INTU	NM_015693.4	MANE Select	c.1063G>C	p.Glu355Gln	missense	Exon 5 of 16	NP_056508.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INTU	ENST00000335251.11	TSL:1 MANE Select	c.1063G>C	p.Glu355Gln	missense	Exon 5 of 16	ENSP00000334003.5	Q9ULD6-1
INTU	ENST00000503952.5	TSL:1	n.1063G>C		non_coding_transcript_exon	Exon 5 of 17	ENSP00000421995.1	Q9ULD6-3
INTU	ENST00000917159.1		c.1063G>C	p.Glu355Gln	missense	Exon 5 of 16	ENSP00000587218.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1386490

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689844

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31106

American (AMR)

AF:

0.00

AC:

AN:

39908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24668

East Asian (EAS)

AF:

0.00

AC:

AN:

37054

South Asian (SAS)

AF:

0.00

AC:

AN:

76274

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5364

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1063630

Other (OTH)

AF:

0.00

AC:

AN:

56880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0019

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

7.0

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.57

REVEL

Benign

0.050

Sift

Benign

0.25

Sift4G

Benign

0.20

Polyphen

0.49

Vest4

0.42

MutPred

0.19

Gain of MoRF binding (P = 0.2168)

MVP

0.68

MPC

0.17

ClinPred

0.89

GERP RS

5.3

Varity_R

0.19

gMVP

0.51

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over