11-129902498-C-A

Variant names:

• chr11-129902498-C-A
• rs1461300656
• NM_199437.2:c.3286G>T

Variant summary

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

The NM_199437.2(PRDM10):​c.3286G>T​(p.Glu1096*) variant causes a stop gained change. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRDM10 NM_199437.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.60
• Publications: 0 publications found

Genes affected

PRDM10 (HGNC:13995): (PR/SET domain 10) The protein encoded by this gene is a transcription factor that contains C2H2-type zinc-fingers. It also contains a positive regulatory domain, which has been found in several other zinc-finger transcription factors including those involved in B cell differentiation and tumor suppression. Studies of the mouse counterpart suggest that this protein may be involved in the development of the central nerve system (CNS), as well as in the pathogenesis of neuronal storage disease. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

PRDM10 Gene-Disease associations (from GenCC):

• Birt-Hogg-Dube syndrome 2

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199437.2. 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
	PRDM10	NM_199437.2	MANE Select	c.3286G>T	p.Glu1096*	stop_gained	Exon 21 of 21	NP_955469.1	Q9NQV6-4
	PRDM10	NM_020228.3		c.3298G>T	p.Glu1100*	stop_gained	Exon 22 of 22	NP_064613.2
	PRDM10	NM_001367893.1		c.3259G>T	p.Glu1087*	stop_gained	Exon 22 of 22	NP_001354822.1	Q9NQV6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM10	ENST00000360871.8	TSL:1 MANE Select	c.3286G>T	p.Glu1096*	stop_gained	Exon 21 of 21	ENSP00000354118.3	Q9NQV6-4
	PRDM10	ENST00000358825.9	TSL:1	c.3298G>T	p.Glu1100*	stop_gained	Exon 22 of 22	ENSP00000351686.5	Q9NQV6-7
	PRDM10	ENST00000526082.5	TSL:1	c.3040G>T	p.Glu1014*	stop_gained	Exon 18 of 18	ENSP00000432237.1	Q9NQV6-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	42
DANN	Uncertain	1.0
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		6.6
Vest4		0.34
GERP RS		5.7
Mutation Taster		=10/190	disease causing

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

dbSNP: rs1461300656; hg19: chr11-129772393;