Menu
GeneBe

10-101580387-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001174084.2(POLL):c.1224T>C(p.Ser408=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,613,466 control chromosomes in the GnomAD database, including 61,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 4747 hom., cov: 33)
Exomes 𝑓: 0.27 ( 56975 hom. )

Consequence

POLL
NM_001174084.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.60
Variant links:
Genes affected
POLL (HGNC:9184): (DNA polymerase lambda) This gene encodes a DNA polymerase. DNA polymerases catalyze DNA-template-directed extension of the 3'-end of a DNA strand. This particular polymerase, which is a member of the X family of DNA polymerases, likely plays a role in non-homologous end joining and other DNA repair processes. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2010]
DPCD (HGNC:24542): (deleted in primary ciliary dyskinesia homolog (mouse)) This gene in mouse encodes a protein that may be involved in the generation and maintenance of ciliated cells. In mouse, expression of this gene increases during ciliated cell differentiation, and disruption of this gene has been linked to primary ciliary dyskinesia. [provided by RefSeq, Jul 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-101580387-A-G is Benign according to our data. Variant chr10-101580387-A-G is described in ClinVar as [Benign]. Clinvar id is 1221687.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.6 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
POLLNM_001174084.2 linkuse as main transcriptc.1224T>C p.Ser408= synonymous_variant 8/9 ENST00000370162.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
POLLENST00000370162.8 linkuse as main transcriptc.1224T>C p.Ser408= synonymous_variant 8/91 NM_001174084.2 P1Q9UGP5-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.241
AC:
36584
AN:
151998
Hom.:
4743
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.185
Gnomad AMI
AF:
0.389
Gnomad AMR
AF:
0.222
Gnomad ASJ
AF:
0.288
Gnomad EAS
AF:
0.0381
Gnomad SAS
AF:
0.157
Gnomad FIN
AF:
0.242
Gnomad MID
AF:
0.263
Gnomad NFE
AF:
0.296
Gnomad OTH
AF:
0.237
GnomAD3 exomes
AF:
0.229
AC:
57291
AN:
250706
Hom.:
7399
AF XY:
0.232
AC XY:
31398
AN XY:
135536
show subpopulations
Gnomad AFR exome
AF:
0.181
Gnomad AMR exome
AF:
0.157
Gnomad ASJ exome
AF:
0.283
Gnomad EAS exome
AF:
0.0342
Gnomad SAS exome
AF:
0.167
Gnomad FIN exome
AF:
0.245
Gnomad NFE exome
AF:
0.296
Gnomad OTH exome
AF:
0.252
GnomAD4 exome
AF:
0.273
AC:
398644
AN:
1461350
Hom.:
56975
Cov.:
35
AF XY:
0.271
AC XY:
196930
AN XY:
727002
show subpopulations
Gnomad4 AFR exome
AF:
0.180
Gnomad4 AMR exome
AF:
0.163
Gnomad4 ASJ exome
AF:
0.291
Gnomad4 EAS exome
AF:
0.0476
Gnomad4 SAS exome
AF:
0.171
Gnomad4 FIN exome
AF:
0.251
Gnomad4 NFE exome
AF:
0.298
Gnomad4 OTH exome
AF:
0.257
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.241
AC:
36602
AN:
152116
Hom.:
4747
Cov.:
33
AF XY:
0.235
AC XY:
17508
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.185
Gnomad4 AMR
AF:
0.222
Gnomad4 ASJ
AF:
0.288
Gnomad4 EAS
AF:
0.0381
Gnomad4 SAS
AF:
0.157
Gnomad4 FIN
AF:
0.242
Gnomad4 NFE
AF:
0.296
Gnomad4 OTH
AF:
0.241
Alfa
AF:
0.284
Hom.:
7184
Bravo
AF:
0.237
Asia WGS
AF:
0.110
AC:
385
AN:
3478
EpiCase
AF:
0.302
EpiControl
AF:
0.292

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
0.051
Dann
Benign
0.49

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: rs3730476; hg19: chr10-103340144; COSMIC: COSV54574937; COSMIC: COSV54574937; API