Variant 7-75542943-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005338.7(HIP1):c.2798C>A(p.Ala933Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HIP1
NM_005338.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

Variant links:

Genes affected

HIP1 (HGNC:4913): (huntingtin interacting protein 1) The product of this gene is a membrane-associated protein that functions in clathrin-mediated endocytosis and protein trafficking within the cell. The encoded protein binds to the huntingtin protein in the brain; this interaction is lost in Huntington's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

HIP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09296277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIP1	NM_005338.7 linkuse as main transcript	c.2798C>A	p.Ala933Asp	missense_variant	28/31	ENST00000336926.11	NP_005329.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIP1	ENST00000336926.11 linkuse as main transcript	c.2798C>A	p.Ala933Asp	missense_variant	28/31	1	NM_005338.7	ENSP00000336747	P1	O00291-1
HIP1	ENST00000616821.4 linkuse as main transcript	c.2711C>A	p.Ala904Asp	missense_variant	28/31	1		ENSP00000484528		O00291-4
HIP1	ENST00000434438.6 linkuse as main transcript	c.2645C>A	p.Ala882Asp	missense_variant	26/29	2		ENSP00000410300		O00291-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 30, 2023

The c.2798C>A (p.A933D) alteration is located in exon 28 (coding exon 28) of the HIP1 gene. This alteration results from a C to A substitution at nucleotide position 2798, causing the alanine (A) at amino acid position 933 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.86

D;D;D

M_CAP

Benign

0.0081

MetaRNN

Benign

0.093

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.12

N;.;.

MutationTaster

Benign

0.94

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.7

N;N;.

REVEL

Benign

0.052

Sift

Benign

0.087

T;T;.

Sift4G

Benign

0.19

T;T;T

Polyphen

0.029

B;.;.

Vest4

0.25

MutPred

0.36

Loss of MoRF binding (P = 0.0806);.;.;

MVP

0.23

MPC

0.53

ClinPred

0.47

GERP RS

4.3

Varity_R

0.16

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over