2-229026025-C-G

Variant names:

• chr2-229026025-C-G
• NM_001100818.2:c.261G>C
• PID1 p.Lys87Asn

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001100818.2(PID1):​c.261G>C​(p.Lys87Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PID1 NM_001100818.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1932849).

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.261G>C	p.Lys87Asn	missense	Exon 3 of 3	NP_001094288.1	Q7Z2X4-4
	PID1	NM_001330156.1		c.360G>C	p.Lys120Asn	missense	Exon 3 of 3	NP_001317085.1	Q7Z2X4-1
	PID1	NM_017933.5		c.354G>C	p.Lys118Asn	missense	Exon 4 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.261G>C	p.Lys87Asn	missense	Exon 3 of 3	ENSP00000375908.3	Q7Z2X4-4
	PID1	ENST00000409462.1	TSL:1	c.114G>C	p.Lys38Asn	missense	Exon 2 of 2	ENSP00000386826.1	Q7Z2X4-3
	PID1	ENST00000354069.6	TSL:3	c.360G>C	p.Lys120Asn	missense	Exon 3 of 3	ENSP00000283937.8	Q7Z2X4-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T
Eigen	Benign	0.027
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.12
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.011	D
Varity_R		0.29
gMVP		0.51
Mutation Taster		=55/45	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-229890741;