Genetic Variant NM_199437.2:c.2959G>A (chr11-129912108-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_199437.2(PRDM10):c.2959G>A(p.Ala987Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000701 in 1,610,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A987P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

PRDM10
NM_199437.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.05

Publications

5 publications found

Variant links:

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

PRDM10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025621504).

BS2

High AC in GnomAd4 at 27 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDM10	NM_199437.2	MANE Select	c.2959G>A	p.Ala987Thr	missense	Exon 18 of 21	NP_955469.1	Q9NQV6-4
PRDM10	NM_020228.3		c.2971G>A	p.Ala991Thr	missense	Exon 19 of 22	NP_064613.2
PRDM10	NM_001367892.1		c.2905G>A	p.Ala969Thr	missense	Exon 19 of 22	NP_001354821.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDM10	ENST00000360871.8	TSL:1 MANE Select	c.2959G>A	p.Ala987Thr	missense	Exon 18 of 21	ENSP00000354118.3	Q9NQV6-4
PRDM10	ENST00000358825.9	TSL:1	c.2971G>A	p.Ala991Thr	missense	Exon 19 of 22	ENSP00000351686.5	Q9NQV6-7
PRDM10	ENST00000526082.5	TSL:1	c.2713G>A	p.Ala905Thr	missense	Exon 15 of 18	ENSP00000432237.1	Q9NQV6-5

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000806

AC:

AN:

248246

AF XY:

0.0000522

show subpopulations

Gnomad AFR exome

AF:

0.000372

Gnomad AMR exome

AF:

0.0000880

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.000995

GnomAD4 exome

AF:

0.0000590

AC:

AN:

1458670

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

725598

show subpopulations

African (AFR)

AF:

0.000660

AC:

AN:

33342

American (AMR)

AF:

0.0000900

AC:

AN:

44448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25998

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39450

South Asian (SAS)

AF:

0.00

AC:

AN:

85870

European-Finnish (FIN)

AF:

0.0000754

AC:

AN:

53042

Middle Eastern (MID)

AF:

0.00261

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

1110530

Other (OTH)

AF:

0.000266

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000177

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41554

American (AMR)

AF:

0.000261

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68008

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000801

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.0000596

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.37

(source)

DANN

Benign

0.88

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.71

M_CAP

Benign

0.0018

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

PhyloP100

-1.1

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.35

REVEL

Benign

0.040

Sift

Benign

0.21

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.032

MVP

0.12

MPC

0.098

ClinPred

0.014

GERP RS

-12

gMVP

0.20

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over