Genetic Variant NM_001377229.1:c.52A>T (chr1-222942875-A-T) – 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_001377229.1(DISP1):c.52A>T(p.Ile18Phe) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I18I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

DISP1
NM_001377229.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Publications

0 publications found

Variant links:

Genes affected

DISP1 (HGNC:19711): (dispatched RND transporter family member 1) The pattern of cellular proliferation and differentiation that leads to normal development of embryonic structures often depends upon the localized production of secreted protein signals. Cells surrounding the source of a particular signal respond in a graded manner according to the effective concentration of the signal, and this response produces the pattern of cell types constituting the mature structure. A novel segment-polarity gene known as dispatched has been identified in Drosophila and its protein product is required for normal Hedgehog (Hh) signaling. This gene is one of two human homologs of Drosophila dispatched and, based on sequence identity to its mouse counterpart, the encoded protein may play an essential role in Hh patterning activities in the early embryo. [provided by RefSeq, Jul 2008]

DISP1 Gene-Disease associations (from GenCC):

holoprosencephaly
Inheritance: SD, AD, AR Classification: SUPPORTIVE, LIMITED Submitted by: Illumina, ClinGen, Orphanet

DISP1 links:

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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=0.40227258).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377229.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DISP1	NM_001377229.1	MANE Select	c.52A>T	p.Ile18Phe	missense	Exon 3 of 9	NP_001364158.1	Q96F81
DISP1	NM_001369594.1		c.52A>T	p.Ile18Phe	missense	Exon 2 of 8	NP_001356523.1	Q96F81
DISP1	NM_001377228.1		c.52A>T	p.Ile18Phe	missense	Exon 2 of 8	NP_001364157.1	Q96F81

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DISP1	ENST00000675850.1	MANE Select	c.52A>T	p.Ile18Phe	missense	Exon 3 of 9	ENSP00000502357.1	Q96F81
DISP1	ENST00000284476.7	TSL:1	c.52A>T	p.Ile18Phe	missense	Exon 2 of 8	ENSP00000284476.6	Q96F81
DISP1	ENST00000482856.1	TSL:1	n.199A>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

9.4

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.049

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.75

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.40

MetaSVM

Uncertain

0.067

MutationAssessor

Uncertain

2.1

PhyloP100

2.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.54

REVEL

Uncertain

0.39

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0080

Polyphen

0.68

Vest4

0.58

MutPred

0.18

Loss of glycosylation at S17 (P = 0.0716)

MVP

0.74

MPC

0.39

ClinPred

0.31

GERP RS

0.83

Varity_R

0.11

gMVP

0.40

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over