rs2303659

Variant names:

• chr11-129951369-C-T
• rs2303659
• NM_199437.2:c.295-3999G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199437.2(PRDM10):​c.295-3999G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 152,178 control chromosomes in the GnomAD database, including 682 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.068 (682 hom., cov: 32)
• Consequence: PRDM10 NM_199437.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

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.295-3999G>A		intron	N/A	NP_955469.1	Q9NQV6-4
	PRDM10	NM_020228.3		c.295-3999G>A		intron	N/A	NP_064613.2
	PRDM10	NM_001367893.1		c.295-3999G>A		intron	N/A	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.295-3999G>A		intron	N/A	ENSP00000354118.3	Q9NQV6-4
	PRDM10	ENST00000358825.9	TSL:1	c.295-3999G>A		intron	N/A	ENSP00000351686.5	Q9NQV6-7
	PRDM10	ENST00000887352.1		c.295-3999G>A		intron	N/A	ENSP00000557411.1

Frequencies

GnomAD3 genomes AF: 0.0678 AC: 10313 AN: 152060 Hom.: 683 Cov.: 32

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0635

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0678 AC: 10322 AN: 152178 Hom.: 682 Cov.: 32 AF XY: 0.0703 AC XY: 5235 AN XY: 74418

African (AFR) AF: 0.0956 AC: 3968 AN: 41498

American (AMR) AF: 0.0729 AC: 1115 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0482 AC: 167 AN: 3468

East Asian (EAS) AF: 0.389 AC: 2000 AN: 5146

South Asian (SAS) AF: 0.0824 AC: 398 AN: 4832

European-Finnish (FIN) AF: 0.0369 AC: 392 AN: 10612

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0309 AC: 2099 AN: 68014

Other (OTH) AF: 0.0633 AC: 134 AN: 2116

Alfa AF: 0.0433 Hom.: 415

Bravo AF: 0.0740

Asia WGS AF: 0.174 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.6
DANN	Benign	0.85
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs2303659; hg19: chr11-129821264;