NM_001174084.2:c.*68C>T

Variant names:

• chr10-101579385-G-A
• rs3730478
• NM_001174084.2:c.*68C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001174084.2(POLL):​c.*68C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0727 in 1,513,876 control chromosomes in the GnomAD database, including 4,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.076 (479 hom., cov: 32)
  • Exomes 𝑓: 0.072 (3825 hom.)
• Consequence: POLL NM_001174084.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.163
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-101579385-G-A is Benign according to our data. Variant chr10-101579385-G-A is described in ClinVar as Benign. ClinVar VariationId is 1279768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174084.2. 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
	POLL	NM_001174084.2	MANE Select	c.*68C>T		3_prime_UTR	Exon 9 of 9	NP_001167555.1	Q9UGP5-1
	POLL	NM_013274.4		c.*68C>T		3_prime_UTR	Exon 9 of 9	NP_037406.1	Q9UGP5-1
	POLL	NM_001174085.2		c.*68C>T		3_prime_UTR	Exon 9 of 9	NP_001167556.1	A8K860

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLL	ENST00000370162.8	TSL:1 MANE Select	c.*68C>T		3_prime_UTR	Exon 9 of 9	ENSP00000359181.3	Q9UGP5-1
	POLL	ENST00000299206.8	TSL:1	c.*68C>T		3_prime_UTR	Exon 9 of 9	ENSP00000299206.4	Q9UGP5-1
	POLL	ENST00000370169.5	TSL:1	c.*68C>T		3_prime_UTR	Exon 8 of 8	ENSP00000359188.1	Q9UGP5-1

Frequencies

GnomAD3 genomes AF: 0.0762 AC: 11591 AN: 152032 Hom.: 477 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0622

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.0580

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0744

Gnomad OTH AF: 0.0626

GnomAD4 exome AF: 0.0723 AC: 98454 AN: 1361726 Hom.: 3825 Cov.: 29 AF XY: 0.0715 AC XY: 47927 AN XY: 670750

African (AFR) AF: 0.105 AC: 3211 AN: 30594

American (AMR) AF: 0.0484 AC: 1591 AN: 32850

Ashkenazi Jewish (ASJ) AF: 0.0506 AC: 1036 AN: 20476

East Asian (EAS) AF: 0.000820 AC: 32 AN: 39026

South Asian (SAS) AF: 0.0423 AC: 3140 AN: 74192

European-Finnish (FIN) AF: 0.0643 AC: 2485 AN: 38664

Middle Eastern (MID) AF: 0.0330 AC: 129 AN: 3908

European-Non Finnish (NFE) AF: 0.0780 AC: 83140 AN: 1065778

Other (OTH) AF: 0.0656 AC: 3690 AN: 56238

GnomAD4 genome AF: 0.0763 AC: 11608 AN: 152150 Hom.: 479 Cov.: 32 AF XY: 0.0741 AC XY: 5509 AN XY: 74386

African (AFR) AF: 0.104 AC: 4312 AN: 41512

American (AMR) AF: 0.0623 AC: 953 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 174 AN: 3468

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5150

South Asian (SAS) AF: 0.0399 AC: 192 AN: 4816

European-Finnish (FIN) AF: 0.0580 AC: 616 AN: 10614

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0743 AC: 5054 AN: 67978

Other (OTH) AF: 0.0676 AC: 143 AN: 2114

Alfa AF: 0.0717 Hom.: 569

Bravo AF: 0.0769

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.75
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs3730478; hg19: chr10-103339142; COSMIC: COSV54574132; COSMIC: COSV54574132;