chr11-112071247-T-C

Variant names:

• chr11-112071247-T-C
• rs1024887283
• NM_138789.4:c.338A>G

Variant summary

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

The NM_138789.4(PIH1D2):​c.338A>G​(p.Asp113Gly) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIH1D2 NM_138789.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15
• Publications: 0 publications found

Genes affected

PIH1D2 (HGNC:25210): (PIH1 domain containing 2) Enables small GTPase binding activity. Predicted to be involved in box C/D snoRNP assembly and rRNA processing. Predicted to be part of R2TP complex and ribonucleoprotein complex. Predicted to be active 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=0.22362122).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138789.4. 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
	PIH1D2	NM_138789.4	MANE Select	c.338A>G	p.Asp113Gly	missense	Exon 4 of 6	NP_620144.1	Q8WWB5-1
	PIH1D2	NM_001439211.1		c.338A>G	p.Asp113Gly	missense	Exon 4 of 6	NP_001426140.1
	PIH1D2	NM_001082619.2		c.338A>G	p.Asp113Gly	missense	Exon 4 of 6	NP_001076088.1	Q8WWB5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIH1D2	ENST00000280350.10	TSL:5 MANE Select	c.338A>G	p.Asp113Gly	missense	Exon 4 of 6	ENSP00000280350.4	Q8WWB5-1
	PIH1D2	ENST00000532211.5	TSL:5	c.338A>G	p.Asp113Gly	missense	Exon 4 of 6	ENSP00000431841.1	Q8WWB5-1
	PIH1D2	ENST00000957365.1		c.338A>G	p.Asp113Gly	missense	Exon 3 of 5	ENSP00000627424.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.077
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.075
Sift	Benign	0.31	T
Sift4G	Benign	0.40	T
Polyphen		0.015	B
Vest4		0.16
MutPred		0.59		Gain of catalytic residue at V114 (P = 0.0678)
MVP		0.31
MPC		0.14
ClinPred		0.15	T
GERP RS		1.3
Varity_R		0.093
gMVP		0.38
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1024887283; hg19: chr11-111941971;