11-66232965-G-T

Variant names:

• chr11-66232965-G-T
• NM_018026.4:c.1737G>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_018026.4(PACS1):​c.1737G>T​(p.Val579Val) 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. V579V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PACS1 NM_018026.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 11-66232965-G-T is Benign according to our data. Variant chr11-66232965-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2080938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.45 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACS1	NM_018026.4	c.1737G>T	p.Val579Val	synonymous_variant	Exon 15 of 24	ENST00000320580.9	NP_060496.2
PACS1	XM_011545162.2	c.1443G>T	p.Val481Val	synonymous_variant	Exon 15 of 24		XP_011543464.2
PACS1	XM_011545164.3	c.1398G>T	p.Val466Val	synonymous_variant	Exon 15 of 24		XP_011543466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACS1	ENST00000320580.9	c.1737G>T	p.Val579Val	synonymous_variant	Exon 15 of 24	1	NM_018026.4	ENSP00000316454.4
PACS1	ENST00000529757.5	c.345G>T	p.Val115Val	synonymous_variant	Exon 4 of 13	1		ENSP00000432858.1
PACS1	ENST00000528935	c.-121G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 4	4		ENSP00000437052.1
PACS1	ENST00000528935	c.-121G>T		5_prime_UTR_variant	Exon 2 of 4	4		ENSP00000437052.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Schuurs-Hoeijmakers syndrome Benign:1

Aug 23, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr11-66000436;