4-120694991-A-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_018699.4(PRDM5):​c.*120T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,207,890 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.011 ( 18 hom., cov: 32)
Exomes 𝑓: 0.012 ( 102 hom. )

Consequence

PRDM5
NM_018699.4 3_prime_UTR

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.610
Variant links:
Genes affected
PRDM5 (HGNC:9349): (PR/SET domain 5) The protein encoded by this gene is a transcription factor of the PR-domain protein family. It contains a PR-domain and multiple zinc finger motifs. Transcription factors of the PR-domain family are known to be involved in cell differentiation and tumorigenesis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 4-120694991-A-G is Benign according to our data. Variant chr4-120694991-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 347429.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0114 (1735/152254) while in subpopulation NFE AF = 0.0153 (1038/67994). AF 95% confidence interval is 0.0145. There are 18 homozygotes in GnomAd4. There are 922 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
BS2
High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRDM5NM_018699.4 linkc.*120T>C 3_prime_UTR_variant Exon 16 of 16 ENST00000264808.8 NP_061169.2 Q9NQX1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRDM5ENST00000264808 linkc.*120T>C 3_prime_UTR_variant Exon 16 of 16 1 NM_018699.4 ENSP00000264808.3 Q9NQX1-1

Frequencies

GnomAD3 genomes
AF:
0.0114
AC:
1735
AN:
152136
Hom.:
18
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00227
Gnomad AMI
AF:
0.0482
Gnomad AMR
AF:
0.0142
Gnomad ASJ
AF:
0.00173
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.0290
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0153
Gnomad OTH
AF:
0.00813
GnomAD4 exome
AF:
0.0116
AC:
12286
AN:
1055636
Hom.:
102
Cov.:
14
AF XY:
0.0114
AC XY:
6207
AN XY:
542180
show subpopulations
Gnomad4 AFR exome
AF:
0.00206
AC:
52
AN:
25270
Gnomad4 AMR exome
AF:
0.00607
AC:
260
AN:
42814
Gnomad4 ASJ exome
AF:
0.00116
AC:
27
AN:
23370
Gnomad4 EAS exome
AF:
0.0000535
AC:
2
AN:
37414
Gnomad4 SAS exome
AF:
0.00229
AC:
175
AN:
76502
Gnomad4 FIN exome
AF:
0.0241
AC:
1106
AN:
45862
Gnomad4 NFE exome
AF:
0.0135
AC:
10191
AN:
753808
Gnomad4 Remaining exome
AF:
0.00985
AC:
463
AN:
47010
Heterozygous variant carriers
0
606
1213
1819
2426
3032
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
314
628
942
1256
1570
<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:
0.0114
AC:
1735
AN:
152254
Hom.:
18
Cov.:
32
AF XY:
0.0124
AC XY:
922
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.00226
AC:
0.00226114
AN:
0.00226114
Gnomad4 AMR
AF:
0.0141
AC:
0.0141454
AN:
0.0141454
Gnomad4 ASJ
AF:
0.00173
AC:
0.00172811
AN:
0.00172811
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.00228
AC:
0.00227838
AN:
0.00227838
Gnomad4 FIN
AF:
0.0290
AC:
0.0290292
AN:
0.0290292
Gnomad4 NFE
AF:
0.0153
AC:
0.0152661
AN:
0.0152661
Gnomad4 OTH
AF:
0.00804
AC:
0.00804163
AN:
0.00804163
Heterozygous variant carriers
0
82
164
247
329
411
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.0127
Hom.:
18
Bravo
AF:
0.00914
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Brittle cornea syndrome 1 Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
Jun 26, 2018
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
8.7
DANN
Benign
0.89
Mutation Taster
=97/3
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs77157999; hg19: chr4-121616146; API