Genetic Variant PRDM7:c.194-46A>C (chr16-90075069-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001098173.2(PRDM7):c.194-46A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 152,140 control chromosomes in the GnomAD database, including 68,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.95 ( 68784 hom., cov: 29)

Exomes 𝑓: 0.93 ( 627710 hom. )

Failed GnomAD Quality Control

Consequence

PRDM7
NM_001098173.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.977

Publications

18 publications found

Variant links:

Genes affected

PRDM7 (HGNC:9351): (PR/SET domain 7) This gene encodes a member of a family of proteins that may have roles in transcription and other nuclear processes. The encoded protein contains a KRAB (Kruppel-associated box) domain -A box and a SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain and may function as a histone methyltransferase. [provided by RefSeq, Aug 2013]

PRDM7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098173.2. 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
	PRDM7	NM_001098173.2	MANE Select	c.194-46A>C		intron	N/A	NP_001091643.1	Q9NQW5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRDM7	ENST00000449207.8	TSL:1 MANE Select	c.194-46A>C	intron	N/A	ENSP00000396732.2	Q9NQW5-3
PRDM7	ENST00000564210.2	TSL:5	n.70-46A>C	intron	N/A	ENSP00000457667.1	H3BUJ3
PRDM7	ENST00000568473.5	TSL:5	n.194-46A>C	intron	N/A	ENSP00000455390.1	A4Q9G9

Frequencies

GnomAD3 genomes

AF:

0.950

AC:

144473

AN:

152022

Hom.:

68725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.987

Gnomad AMI

AF:

0.890

Gnomad AMR

AF:

0.975

Gnomad ASJ

AF:

0.909

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.989

Gnomad FIN

AF:

0.935

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.921

Gnomad OTH

AF:

0.955

GnomAD2 exomes

AF:

0.946

AC:

234764

AN:

248184

AF XY:

0.947

show subpopulations

Gnomad AFR exome

AF:

0.989

Gnomad AMR exome

AF:

0.979

Gnomad ASJ exome

AF:

0.907

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.931

Gnomad NFE exome

AF:

0.917

Gnomad OTH exome

AF:

0.943

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.929

AC:

1349761

AN:

1452528

Hom.:

627710

Cov.:

AF XY:

0.931

AC XY:

673137

AN XY:

723170

show subpopulations

African (AFR)

AF:

0.990

AC:

32963

AN:

33288

American (AMR)

AF:

0.979

AC:

43696

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.908

AC:

23662

AN:

26070

East Asian (EAS)

AF:

1.00

AC:

39646

AN:

39646

South Asian (SAS)

AF:

0.985

AC:

84718

AN:

86034

European-Finnish (FIN)

AF:

0.932

AC:

49731

AN:

53362

Middle Eastern (MID)

AF:

0.977

AC:

5617

AN:

5750

European-Non Finnish (NFE)

AF:

0.918

AC:

1013352

AN:

1103644

Other (OTH)

AF:

0.938

AC:

56376

AN:

60086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

4988

9976

14965

19953

24941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21322

42644

63966

85288

106610

<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:

0.950

AC:

144591

AN:

152140

Hom.:

68784

Cov.:

AF XY:

0.953

AC XY:

70844

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.987

AC:

40951

AN:

41502

American (AMR)

AF:

0.975

AC:

14919

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.909

AC:

3156

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5160

AN:

5162

South Asian (SAS)

AF:

0.989

AC:

4761

AN:

4816

European-Finnish (FIN)

AF:

0.935

AC:

9898

AN:

10584

Middle Eastern (MID)

AF:

0.983

AC:

287

AN:

292

European-Non Finnish (NFE)

AF:

0.921

AC:

62632

AN:

67994

Other (OTH)

AF:

0.955

AC:

2017

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

356

712

1068

1424

1780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.933

Hom.:

103001

Bravo

AF:

0.954

Asia WGS

AF:

0.989

AC:

3440

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.4

(source)

DANN

Benign

0.72

PhyloP100

-0.98

Mutation Taster

=100/0

polymorphism (auto)

(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