2-229155892-A-C

Variant names:

• chr2-229155892-A-C
• NM_001100818.2:c.103T>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001100818.2(PID1):​c.103T>G​(p.Phe35Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PID1 NM_001100818.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.76
• Publications: 0 publications found

Genes affected

PID1 (HGNC:26084): (phosphotyrosine interaction domain containing 1) Involved in several processes, including mitochondrion morphogenesis; negative regulation of phosphate metabolic process; and positive regulation of macromolecule metabolic process. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.804

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100818.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PID1	NM_001100818.2	MANE Select	c.103T>G	p.Phe35Val	missense	Exon 2 of 3	NP_001094288.1	Q7Z2X4-4
	PID1	NM_001330156.1		c.202T>G	p.Phe68Val	missense	Exon 2 of 3	NP_001317085.1	Q7Z2X4-1
	PID1	NM_017933.5		c.196T>G	p.Phe66Val	missense	Exon 3 of 4	NP_060403.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PID1	ENST00000392055.8	TSL:2 MANE Select	c.103T>G	p.Phe35Val	missense	Exon 2 of 3	ENSP00000375908.3	Q7Z2X4-4
	PID1	ENST00000409462.1	TSL:1	c.30+115122T>G		intron	N/A	ENSP00000386826.1	Q7Z2X4-3
	PID1	ENST00000354069.6	TSL:3	c.202T>G	p.Phe68Val	missense	Exon 2 of 3	ENSP00000283937.8	Q7Z2X4-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.69	N
PhyloP100		8.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.53		Loss of stability (P = 0.2399)
MVP		0.37
MPC		0.27
ClinPred		0.89	D
GERP RS		5.7
Varity_R		0.43
gMVP		0.60
Mutation Taster		=22/78	disease causing

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

Other links and lift over

hg19: chr2-230020608;