6-34529748-A-C

Position:

• chr6-34529748-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020804.5(PACSIN1):​c.695A>C​(p.Glu232Ala) 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 benign outcome for this variant. 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: 7.37

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35336566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACSIN1	NM_020804.5	c.695A>C	p.Glu232Ala	missense_variant	6/10	ENST00000244458.7	NP_065855.1
PACSIN1	NM_001199583.3	c.695A>C	p.Glu232Ala	missense_variant	6/10		NP_001186512.1
PACSIN1	XM_011514541.2	c.695A>C	p.Glu232Ala	missense_variant	6/10		XP_011512843.1
PACSIN1	XM_047418689.1	c.695A>C	p.Glu232Ala	missense_variant	6/10		XP_047274645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACSIN1	ENST00000244458.7	c.695A>C	p.Glu232Ala	missense_variant	6/10	1	NM_020804.5	ENSP00000244458.2
PACSIN1	ENST00000538621.2	c.695A>C	p.Glu232Ala	missense_variant	6/10	1		ENSP00000439639.1
PACSIN1	ENST00000620693.4	c.695A>C	p.Glu232Ala	missense_variant	6/10	1		ENSP00000484060.1
PACSIN1	ENST00000374043.6	c.569A>C	p.Glu190Ala	missense_variant	6/10	1		ENSP00000363155.1

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 17, 2023

The c.695A>C (p.E232A) alteration is located in exon 6 (coding exon 5) of the PACSIN1 gene. This alteration results from a A to C substitution at nucleotide position 695, causing the glutamic acid (E) at amino acid position 232 to be replaced by an alanine (A). 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	0.15
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D;T;D;D
Eigen	Benign	0.16
Eigen_PC	Benign	0.091
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	.;D;.;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M;.;M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.5	.;D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0080	.;D;D;D
Sift4G	Uncertain	0.036	D;D;D;D
Polyphen		0.84	P;.;P;P
Vest4		0.46
MutPred		0.35		Loss of disorder (P = 0.0279);.;Loss of disorder (P = 0.0279);Loss of disorder (P = 0.0279);
MVP		0.55
MPC		0.70
ClinPred		0.84	D
GERP RS		2.8
Varity_R		0.37
gMVP		0.18

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: chr6-34497525;