6-34527411-A-G

Position:

• chr6-34527411-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020804.5(PACSIN1):​c.143A>G​(p.Glu48Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PACSIN1 NM_020804.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.20

Genes affected

PACSIN1 (HGNC:8570): (protein kinase C and casein kinase substrate in neurons 1) Enables phospholipid binding activity. Involved in plasma membrane tubulation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PACSIN1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.899

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACSIN1	NM_020804.5	c.143A>G	p.Glu48Gly	missense_variant	3/10	ENST00000244458.7	NP_065855.1
PACSIN1	NM_001199583.3	c.143A>G	p.Glu48Gly	missense_variant	3/10		NP_001186512.1
PACSIN1	XM_011514541.2	c.143A>G	p.Glu48Gly	missense_variant	3/10		XP_011512843.1
PACSIN1	XM_047418689.1	c.143A>G	p.Glu48Gly	missense_variant	3/10		XP_047274645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACSIN1	ENST00000244458.7	c.143A>G	p.Glu48Gly	missense_variant	3/10	1	NM_020804.5	ENSP00000244458.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.143A>G (p.E48G) alteration is located in exon 3 (coding exon 2) of the PACSIN1 gene. This alteration results from a A to G substitution at nucleotide position 143, causing the glutamic acid (E) at amino acid position 48 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;T;T;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	.;D;.;D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Pathogenic	3.6	H;.;H;H
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-6.3	.;D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	.;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		0.96	D;.;D;D
Vest4		0.92
MutPred		0.71		Gain of MoRF binding (P = 0.0358);.;Gain of MoRF binding (P = 0.0358);Gain of MoRF binding (P = 0.0358);
MVP		0.60
MPC		2.7
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.92
gMVP		0.87

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: chr6-34495188;