NM_199437.2:c.3098A>C

Variant names:

• chr11-129910541-T-G
• rs141740226
• NM_199437.2:c.3098A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. 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. 15/20 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
• 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 -10 ACMG points.

• 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 VariationId is 2642544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 330 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM10	NM_199437.2	MANE Select	c.3098A>C	p.Gln1033Pro	missense	Exon 19 of 21	NP_955469.1	Q9NQV6-4
	PRDM10	NM_020228.3		c.3110A>C	p.Gln1037Pro	missense	Exon 20 of 22	NP_064613.2
	PRDM10	NM_001367893.1		c.3071A>C	p.Gln1024Pro	missense	Exon 20 of 22	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.3098A>C	p.Gln1033Pro	missense	Exon 19 of 21	ENSP00000354118.3	Q9NQV6-4
	PRDM10	ENST00000358825.9	TSL:1	c.3110A>C	p.Gln1037Pro	missense	Exon 20 of 22	ENSP00000351686.5	Q9NQV6-7
	PRDM10	ENST00000526082.5	TSL:1	c.2852A>C	p.Gln951Pro	missense	Exon 16 of 18	ENSP00000432237.1	Q9NQV6-5

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

GnomAD2 exomes AF: 0.00298 AC: 745 AN: 250096 AF XY: 0.00292

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 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

African (AFR) AF: 0.000897 AC: 30 AN: 33458

American (AMR) AF: 0.00197 AC: 88 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 437 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.00227 AC: 196 AN: 86238

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53306

Middle Eastern (MID) AF: 0.0109 AC: 63 AN: 5766

European-Non Finnish (NFE) AF: 0.00327 AC: 3631 AN: 1111470

Other (OTH) AF: 0.00383 AC: 231 AN: 60350

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

African (AFR) AF: 0.000457 AC: 19 AN: 41546

American (AMR) AF: 0.00176 AC: 27 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00309 AC: 210 AN: 68008

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00315 Hom.: 4

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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
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
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.019
Sift	Benign	0.038	D
Sift4G	Benign	0.074	T
Polyphen		0.0	B
Vest4		0.31
MVP		0.068
MPC		0.12
ClinPred		0.037	T
GERP RS		1.2
gMVP		0.43
Mutation Taster		=98/2	polymorphism

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: rs141740226; hg19: chr11-129780436;