11-66070560-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_018026.4(PACS1):c.74T>G(p.Val25Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,441,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

PACS1
NM_018026.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.475

Publications

0 publications found

Variant links:

Genes affected

PACS1 (HGNC:30032): (phosphofurin acidic cluster sorting protein 1) This gene encodes a protein with a putative role in the localization of trans-Golgi network (TGN) membrane proteins. Mouse and rat homologs have been identified and studies of the homologous rat protein indicate a role in directing TGN localization of furin by binding to the protease's phosphorylated cytosolic domain. In addition, the human protein plays a role in HIV-1 Nef-mediated downregulation of cell surface MHC-I molecules to the TGN, thereby enabling HIV-1 to escape immune surveillance. [provided by RefSeq, Jul 2008]

PACS1 Gene-Disease associations (from GenCC):

Schuurs-Hoeijmakers syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, ClinGen

PACS1 links:

ENSG00000255038 (HGNC:):

ENSG00000255038 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.088832855).

BP6

Variant 11-66070560-T-G is Benign according to our data. Variant chr11-66070560-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1321766.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018026.4. 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
	PACS1	NM_018026.4	MANE Select	c.74T>G	p.Val25Gly	missense	Exon 1 of 24	NP_060496.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PACS1	ENST00000320580.9	TSL:1 MANE Select	c.74T>G	p.Val25Gly	missense	Exon 1 of 24	ENSP00000316454.4	Q6VY07-1
PACS1	ENST00000527224.1	TSL:2	n.198T>G		non_coding_transcript_exon	Exon 1 of 7
ENSG00000255038	ENST00000830157.1		n.29+470A>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

148932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000597

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000232

AC:

AN:

1292880

Hom.:

Cov.:

AF XY:

0.00000314

AC XY:

AN XY:

637106

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25912

American (AMR)

AF:

0.00

AC:

AN:

22006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21770

East Asian (EAS)

AF:

0.00

AC:

AN:

27672

South Asian (SAS)

AF:

0.00

AC:

AN:

68884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3822

European-Non Finnish (NFE)

AF:

0.00000289

AC:

AN:

1036960

Other (OTH)

AF:

0.00

AC:

AN:

53440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

AF:

0.0000269

AC:

AN:

148932

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72656

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40278

American (AMR)

AF:

0.00

AC:

AN:

15098

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

4980

South Asian (SAS)

AF:

0.00

AC:

AN:

4716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.0000597

AC:

AN:

66962

Other (OTH)

AF:

0.00

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000843

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.059

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.022

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.26

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

-0.47

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.14

REVEL

Benign

0.036

Sift

Pathogenic

0.0

Sift4G

Benign

0.37

Polyphen

0.022

Vest4

0.13

MutPred

0.22

Loss of sheet (P = 0.0228)

MVP

0.10

MPC

1.5

ClinPred

0.24

GERP RS

2.0

PromoterAI

-0.0085

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.23

gMVP

0.094

Mutation Taster

=98/2

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over