rs143934715

Variant names:

• chr2-229025910-C-A
• rs143934715
• NM_001100818.2:c.376G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-229025910-C-A
• chr2-229025910-C-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.376G>T​(p.Asp126Tyr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D126H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PID1 NM_001100818.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43
• 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, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PID1	NM_001100818.2	c.376G>T	p.Asp126Tyr	missense_variant	Exon 3 of 3	ENST00000392055.8	NP_001094288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PID1	ENST00000392055.8	c.376G>T	p.Asp126Tyr	missense_variant	Exon 3 of 3	2	NM_001100818.2	ENSP00000375908.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	.;.;.;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.0086	T
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.9	.;.;.;L
PhyloP100		7.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.83
MutPred		0.49		.;.;.;Loss of disorder (P = 0.0619);
MVP		0.51
MPC		0.58
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.51
gMVP		0.69
Mutation Taster		=10/90	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

dbSNP: rs143934715; hg19: chr2-229890626;