chr11-129910541-T-G

Position:

• chr11-129910541-T-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_199437.2(PRDM10):​c.3098A>C​(p.Gln1033Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00311 in 1,613,372 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (25 hom.)
• Consequence: PRDM10 NM_199437.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.83

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 -9 ACMG points.

• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PRDM10. . Gene score misZ 3.2778 (greater than the threshold 3.09). Trascript score misZ 3.7552 (greater than threshold 3.09). GenCC has associacion of gene with Birt-Hogg-Dube syndrome 2.
• BP4: Computational evidence support a benign effect (MetaRNN=0.00473091).
• BP6: Variant 11-129910541-T-G is Benign according to our data. Variant chr11-129910541-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2642544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 330 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM10	NM_199437.2	c.3098A>C	p.Gln1033Pro	missense_variant	19/21	ENST00000360871.8	NP_955469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM10	ENST00000360871.8	c.3098A>C	p.Gln1033Pro	missense_variant	19/21	1	NM_199437.2	ENSP00000354118	P4

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 328 AN: 152148 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00309

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00298 AC: 745 AN: 250096 Hom.: 10 AF XY: 0.00292 AC XY: 395 AN XY: 135414

Gnomad AFR exome AF: 0.000877

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.0151

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00219

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.00360

Gnomad OTH exome AF: 0.00508

GnomAD4 exome AF: 0.00321 AC: 4692 AN: 1461106 Hom.: 25 Cov.: 31 AF XY: 0.00323 AC XY: 2345 AN XY: 726896

Gnomad4 AFR exome AF: 0.000897

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.0167

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00227

Gnomad4 FIN exome AF: 0.000281

Gnomad4 NFE exome AF: 0.00327

Gnomad4 OTH exome AF: 0.00383

GnomAD4 genome AF: 0.00217 AC: 330 AN: 152266 Hom.: 1 Cov.: 33 AF XY: 0.00210 AC XY: 156 AN XY: 74454

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00309

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00321 Hom.: 0

Bravo AF: 0.00241

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00454 AC: 39

ExAC AF: 0.00291 AC: 353

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

PRDM10: PP2, BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.95
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.62
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.69	T;T;T;T;T;T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.0047	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.73	D;D;N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.78	N;N;N;N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.038	D;D;D;D;D;D;D
Sift4G	Benign	0.074	T;T;T;D;D;T;D
Polyphen		0.0, 0.0010	.;B;.;B;.;B;.
Vest4		0.31
MVP		0.068
MPC		0.12
ClinPred		0.037	T
GERP RS		1.2
gMVP		0.43

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: rs141740226; hg19: chr11-129780436;