11-129910517-T-G

Variant names:

• chr11-129910517-T-G
• rs751925955
• NM_199437.2:c.3122A>C

Variant summary

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

The NM_199437.2(PRDM10):​c.3122A>C​(p.His1041Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. H1041R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PRDM10 NM_199437.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.74
• 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.3122A>C	p.His1041Pro	missense	Exon 19 of 21	NP_955469.1	Q9NQV6-4
	PRDM10	NM_020228.3		c.3134A>C	p.His1045Pro	missense	Exon 20 of 22	NP_064613.2
	PRDM10	NM_001367893.1		c.3095A>C	p.His1032Pro	missense	Exon 20 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.3122A>C	p.His1041Pro	missense	Exon 19 of 21	ENSP00000354118.3	Q9NQV6-4
	PRDM10	ENST00000358825.9	TSL:1	c.3134A>C	p.His1045Pro	missense	Exon 20 of 22	ENSP00000351686.5	Q9NQV6-7
	PRDM10	ENST00000526082.5	TSL:1	c.2876A>C	p.His959Pro	missense	Exon 16 of 18	ENSP00000432237.1	Q9NQV6-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.2	T
PhyloP100		5.7
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.059	T
Polyphen		0.93	P
Vest4		0.69
MVP		0.23
MPC		0.48
ClinPred		0.86	D
GERP RS		5.8
gMVP		0.50
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: rs751925955; hg19: chr11-129780412;