Genetic Variant HID1:p.Leu8Pro (chr17-74972634-A-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_030630.3(HID1):c.23T>C(p.Leu8Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000394 in 1,396,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

HID1
NM_030630.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76

Publications

0 publications found

Variant links:

Genes affected

HID1 (HGNC:15736): (HID1 domain containing) Located in Golgi cisterna; cytoplasmic microtubule; and cytosol. Is extrinsic component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

HID1 links:

HID1-AS1 (HGNC:51181): (HID1 antisense RNA 1)

HID1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.855

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030630.3. 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
	HID1	NM_030630.3	MANE Select	c.23T>C	p.Leu8Pro	missense	Exon 1 of 19	NP_085133.1	Q8IV36-1
	HID1-AS1	NR_110878.1		n.104+1842A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HID1	ENST00000425042.7	TSL:1 MANE Select	c.23T>C	p.Leu8Pro	missense	Exon 1 of 19	ENSP00000413520.2	Q8IV36-1
HID1	ENST00000879343.1		c.23T>C	p.Leu8Pro	missense	Exon 1 of 19	ENSP00000549402.1
HID1	ENST00000879342.1		c.23T>C	p.Leu8Pro	missense	Exon 1 of 19	ENSP00000549401.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000658

AC:

AN:

152078

AF XY:

0.0000125

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000173

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000394

AC:

AN:

1396440

Hom.:

Cov.:

AF XY:

0.0000348

AC XY:

AN XY:

688856

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31298

American (AMR)

AF:

0.00

AC:

AN:

35564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25074

East Asian (EAS)

AF:

0.00

AC:

AN:

35522

South Asian (SAS)

AF:

0.00

AC:

AN:

78838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.0000501

AC:

AN:

1077604

Other (OTH)

AF:

0.0000173

AC:

AN:

57848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.68

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

-0.036

MutationAssessor

Pathogenic

3.0

PhyloP100

4.8

PrimateAI

Pathogenic

0.95

PROVEAN

Pathogenic

-5.3

REVEL

Pathogenic

0.77

Sift

Benign

0.035

Sift4G

Uncertain

0.015

Polyphen

0.94

Vest4

0.87

MutPred

0.69

Gain of disorder (P = 0.0099)

MVP

0.40

MPC

1.4

ClinPred

0.97

GERP RS

3.5

PromoterAI

0.024

Neutral

(source)

Varity_R

0.89

gMVP

0.86

Mutation Taster

=14/86

disease causing

(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

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