chr1-212365361-G-A

Variant names:

• chr1-212365361-G-A
• NM_018252.3:c.907C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018252.3(PACC1):​c.907C>T​(p.Pro303Ser) variant causes a missense change involving the alteration of a conserved nucleotide. 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: PACC1 NM_018252.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.64
• Publications: 0 publications found

Genes affected

PACC1 (HGNC:25593): (proton activated chloride channel 1) Enables pH-gated chloride channel activity. Involved in chloride transport. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACC1	NM_018252.3	c.907C>T	p.Pro303Ser	missense_variant	Exon 8 of 8	ENST00000261455.9	NP_060722.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACC1	ENST00000261455.9	c.907C>T	p.Pro303Ser	missense_variant	Exon 8 of 8	1	NM_018252.3	ENSP00000261455.4
PACC1	ENST00000535273.2	c.1090C>T	p.Pro364Ser	missense_variant	Exon 9 of 9	2		ENSP00000438863.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1090C>T (p.P364S) alteration is located in exon 9 (coding exon 9) of the TMEM206 gene. This alteration results from a C to T substitution at nucleotide position 1090, causing the proline (P) at amino acid position 364 to be replaced by a serine (S). 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	0.24
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.1	M;.
PhyloP100		7.6
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-6.9	D;D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.011	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.60
MutPred		0.84		Loss of glycosylation at T300 (P = 0.0642);.;
MVP		0.38
MPC		0.81
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.72
gMVP		0.65
Mutation Taster		=20/80	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-212538703;