11-112073102-T-G

Variant names:

• chr11-112073102-T-G
• NM_138789.4:c.73A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138789.4(PIH1D2):​c.73A>C​(p.Ser25Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 4.79
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27646294).

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.73A>C	p.Ser25Arg	missense	Exon 2 of 6	NP_620144.1	Q8WWB5-1
	PIH1D2	NM_001439211.1		c.73A>C	p.Ser25Arg	missense	Exon 2 of 6	NP_001426140.1
	PIH1D2	NM_001082619.2		c.73A>C	p.Ser25Arg	missense	Exon 2 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.73A>C	p.Ser25Arg	missense	Exon 2 of 6	ENSP00000280350.4	Q8WWB5-1
	PIH1D2	ENST00000532211.5	TSL:5	c.73A>C	p.Ser25Arg	missense	Exon 2 of 6	ENSP00000431841.1	Q8WWB5-1
	PIH1D2	ENST00000957365.1		c.73A>C	p.Ser25Arg	missense	Exon 1 of 5	ENSP00000627424.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Uncertain	0.43
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.020	D
Polyphen		0.99	D
Vest4		0.28
MutPred		0.48		Loss of disorder (P = 0.1306)
MVP		0.66
MPC		0.26
ClinPred		0.91	D
GERP RS		5.0
PromoterAI		0.048	Neutral
Varity_R		0.31
gMVP		0.43
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-111943826;