dbSNP rs8070488: HGS:p.Pro595Pro (chr17-81696901-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004712.5(HGS):c.1785T>C(p.Pro595Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,608,460 control chromosomes in the GnomAD database, including 41,440 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5303 hom., cov: 33)

Exomes 𝑓: 0.22 ( 36137 hom. )

Consequence

HGS
NM_004712.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.42

Publications

30 publications found

Variant links:

Genes affected

HGS (HGNC:4897): (hepatocyte growth factor-regulated tyrosine kinase substrate) The protein encoded by this gene regulates endosomal sorting and plays a critical role in the recycling and degradation of membrane receptors. The encoded protein sorts monoubiquitinated membrane proteins into the multivesicular body, targeting these proteins for lysosome-dependent degradation. [provided by RefSeq, Dec 2010]

HGS links:

ENSG00000275902 (HGNC:):

ENSG00000275902 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP7

Synonymous conserved (PhyloP=-6.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HGS	NM_004712.5 link	c.1785T>C	p.Pro595Pro	synonymous_variant	Exon 18 of 22	ENST00000329138.9	NP_004703.1	O14964-1A0A0S2Z4R4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HGS	ENST00000329138.9 link	c.1785T>C	p.Pro595Pro	synonymous_variant	Exon 18 of 22	1	NM_004712.5	ENSP00000331201.4		O14964-1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38508

AN:

151956

Hom.:

5280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.259

GnomAD2 exomes

AF:

0.208

AC:

51092

AN:

245384

AF XY:

0.205

show subpopulations

Gnomad AFR exome

AF:

0.368

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.216

Gnomad FIN exome

AF:

0.222

Gnomad NFE exome

AF:

0.219

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.219

AC:

318745

AN:

1456384

Hom.:

36137

Cov.:

AF XY:

0.216

AC XY:

156831

AN XY:

724578

show subpopulations

African (AFR)

AF:

0.381

AC:

12738

AN:

33436

American (AMR)

AF:

0.142

AC:

6318

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

4621

AN:

26076

East Asian (EAS)

AF:

0.265

AC:

10519

AN:

39666

South Asian (SAS)

AF:

0.162

AC:

13962

AN:

86160

European-Finnish (FIN)

AF:

0.219

AC:

10751

AN:

49102

Middle Eastern (MID)

AF:

0.253

AC:

1460

AN:

5760

European-Non Finnish (NFE)

AF:

0.220

AC:

244682

AN:

1111268

Other (OTH)

AF:

0.227

AC:

13694

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

13442

26884

40326

53768

67210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8596

17192

25788

34384

42980

<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

AF:

0.254

AC:

38572

AN:

152076

Hom.:

5303

Cov.:

AF XY:

0.250

AC XY:

18559

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.368

AC:

15263

AN:

41500

American (AMR)

AF:

0.193

AC:

2944

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

598

AN:

3462

East Asian (EAS)

AF:

0.219

AC:

1130

AN:

5156

South Asian (SAS)

AF:

0.165

AC:

795

AN:

4806

European-Finnish (FIN)

AF:

0.213

AC:

2256

AN:

10582

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14747

AN:

67964

Other (OTH)

AF:

0.257

AC:

542

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1508

3016

4524

6032

7540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.228

Hom.:

5291

Bravo

AF:

0.260

Asia WGS

AF:

0.203

AC:

705

AN:

3478

EpiCase

AF:

0.219

EpiControl

AF:

0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.017

(source)

DANN

Benign

0.39

PhyloP100

-6.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over