chr6-34529407-C-G

Position:

• chr6-34529407-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020804.5(PACSIN1):​c.467C>G​(p.Ala156Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PACSIN1 NM_020804.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.11

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACSIN1	NM_020804.5	c.467C>G	p.Ala156Gly	missense_variant	5/10	ENST00000244458.7	NP_065855.1
PACSIN1	NM_001199583.3	c.467C>G	p.Ala156Gly	missense_variant	5/10		NP_001186512.1
PACSIN1	XM_011514541.2	c.467C>G	p.Ala156Gly	missense_variant	5/10		XP_011512843.1
PACSIN1	XM_047418689.1	c.467C>G	p.Ala156Gly	missense_variant	5/10		XP_047274645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACSIN1	ENST00000244458.7	c.467C>G	p.Ala156Gly	missense_variant	5/10	1	NM_020804.5	ENSP00000244458.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

May 09, 2022

The c.467C>G (p.A156G) alteration is located in exon 5 (coding exon 4) of the PACSIN1 gene. This alteration results from a C to G substitution at nucleotide position 467, causing the alanine (A) at amino acid position 156 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	Benign	0.13
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;T;D;D
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	.;D;.;D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.55	D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.6	M;.;M;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.9	.;D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0030	.;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		0.88	P;.;P;P
Vest4		0.60
MutPred		0.38		Loss of stability (P = 0.0068);.;Loss of stability (P = 0.0068);Loss of stability (P = 0.0068);
MVP		0.53
MPC		0.59
ClinPred		0.97	D
GERP RS		3.8
Varity_R		0.70
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-34497184;