NM_020362.5:c.52C>T

Variant names:

• chr1-23778567-C-T
• NM_020362.5:c.52C>T

Variant summary

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

The NM_020362.5(PITHD1):​c.52C>T​(p.Arg18Trp) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PITHD1 NM_020362.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98
• Publications: 0 publications found

Genes affected

PITHD1 (HGNC:25022): (PITH domain containing 1) Involved in positive regulation of megakaryocyte differentiation and positive regulation of transcription, DNA-templated. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ELOA-AS1 (HGNC:50582): (ELOA antisense RNA 1)

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=0.18936774).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020362.5. 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
	PITHD1	NM_020362.5	MANE Select	c.52C>T	p.Arg18Trp	missense	Exon 1 of 6	NP_065095.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITHD1	ENST00000246151.9	TSL:1 MANE Select	c.52C>T	p.Arg18Trp	missense	Exon 1 of 6	ENSP00000246151.4	Q9GZP4-1
	PITHD1	ENST00000873427.1		c.52C>T	p.Arg18Trp	missense	Exon 1 of 6	ENSP00000543486.1
	ELOA-AS1	ENST00000427796.6	TSL:1	n.-242G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1191188 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 576964

African (AFR) AF: 0.00 AC: 0 AN: 23744

American (AMR) AF: 0.00 AC: 0 AN: 9862

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16614

East Asian (EAS) AF: 0.00 AC: 0 AN: 27138

South Asian (SAS) AF: 0.00 AC: 0 AN: 48362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3350

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 983780

Other (OTH) AF: 0.00 AC: 0 AN: 48650

GnomAD4 genome Cov.: 31

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	Benign	0.21
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.0036
Eigen_PC	Benign	0.078
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.0
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.17
Sift	Benign	0.048	D
Sift4G	Uncertain	0.019	D
Polyphen		0.96	D
Vest4		0.22
MutPred		0.35		Loss of disorder (P = 0.0029)
MVP		0.67
MPC		2.3
ClinPred		0.85	D
GERP RS		5.3
PromoterAI		-0.0046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.31
Mutation Taster		=92/8	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

Other links and lift over

hg19: chr1-24105057;