11-129951369-C-T

Position:

• chr11-129951369-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM10	NM_199437.2	c.295-3999G>A		intron_variant		ENST00000360871.8	NP_955469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM10	ENST00000360871.8	c.295-3999G>A		intron_variant		1	NM_199437.2	ENSP00000354118	P4

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

Gnomad4 AFR AF: 0.0956

Gnomad4 AMR AF: 0.0729

Gnomad4 ASJ AF: 0.0482

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.0824

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.0309

Gnomad4 OTH AF: 0.0633

Alfa AF: 0.0418 Hom.: 314

Bravo AF: 0.0740

Asia WGS AF: 0.174 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.6
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs2303659; hg19: chr11-129821264;