7-75582098-A-T

Variant names:

• chr7-75582098-A-T
• rs237238
• NM_005338.7:c.519T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005338.7(HIP1):​c.519T>A​(p.Ala173Ala) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. A173A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HIP1 NM_005338.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 23 publications found

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]

ENSG00000294540 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-1.8 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005338.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIP1	NM_005338.7	MANE Select	c.519T>A	p.Ala173Ala	synonymous	Exon 6 of 31	NP_005329.3
	HIP1	NM_001382445.1		c.432T>A	p.Ala144Ala	synonymous	Exon 6 of 31	NP_001369374.1
	HIP1	NM_001382444.1		c.417T>A	p.Ala139Ala	synonymous	Exon 6 of 31	NP_001369373.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIP1	ENST00000336926.11	TSL:1 MANE Select	c.519T>A	p.Ala173Ala	synonymous	Exon 6 of 31	ENSP00000336747.6
	HIP1	ENST00000616821.4	TSL:1	c.432T>A	p.Ala144Ala	synonymous	Exon 6 of 31	ENSP00000484528.1
	HIP1	ENST00000434438.6	TSL:2	c.519T>A	p.Ala173Ala	synonymous	Exon 6 of 29	ENSP00000410300.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		-1.8

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

dbSNP: rs237238; hg19: chr7-75211414;