chr11-129916830-G-C

Variant names:

• chr11-129916830-G-C
• rs3734070
• NM_199437.2:c.2325+297C>G

Variant summary

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

The NM_199437.2(PRDM10):​c.2325+297C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,924 control chromosomes in the GnomAD database, including 7,188 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 0.30 (7188 hom., cov: 32)
• Consequence: PRDM10 NM_199437.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM10	NM_199437.2	MANE Select	c.2325+297C>G		intron	N/A	NP_955469.1
	PRDM10	NM_020228.3		c.2337+297C>G		intron	N/A	NP_064613.2
	PRDM10	NM_001367893.1		c.2337+297C>G		intron	N/A	NP_001354822.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM10	ENST00000360871.8	TSL:1 MANE Select	c.2325+297C>G		intron	N/A	ENSP00000354118.3
	PRDM10	ENST00000358825.9	TSL:1	c.2337+297C>G		intron	N/A	ENSP00000351686.5
	PRDM10	ENST00000526082.5	TSL:1	c.2079+297C>G		intron	N/A	ENSP00000432237.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46278 AN: 151806 Hom.: 7191 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.305 AC: 46275 AN: 151924 Hom.: 7188 Cov.: 32 AF XY: 0.302 AC XY: 22397 AN XY: 74250

African (AFR) AF: 0.299 AC: 12361 AN: 41406

American (AMR) AF: 0.243 AC: 3716 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1230 AN: 5168

South Asian (SAS) AF: 0.289 AC: 1392 AN: 4820

European-Finnish (FIN) AF: 0.327 AC: 3441 AN: 10518

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.320 AC: 21742 AN: 67954

Other (OTH) AF: 0.318 AC: 673 AN: 2114

Alfa AF: 0.176 Hom.: 331

Bravo AF: 0.297

Asia WGS AF: 0.269 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.56
PhyloP100		-0.28
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: rs3734070; hg19: chr11-129786725;