rs149081648

Variant names:

• chr10-101580286-C-G
• rs149081648
• NM_001174084.2:c.1325G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-101580286-C-G
• chr10-101580286-C-A
• chr10-101580286-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001174084.2(POLL):​c.1325G>C​(p.Gly442Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: POLL NM_001174084.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.1325G>C	p.Gly442Ala	missense	Exon 8 of 9	NP_001167555.1	Q9UGP5-1
	POLL	NM_013274.4		c.1325G>C	p.Gly442Ala	missense	Exon 8 of 9	NP_037406.1	Q9UGP5-1
	POLL	NM_001174085.2		c.1049G>C	p.Gly350Ala	missense	Exon 8 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.1325G>C	p.Gly442Ala	missense	Exon 8 of 9	ENSP00000359181.3	Q9UGP5-1
	POLL	ENST00000299206.8	TSL:1	c.1325G>C	p.Gly442Ala	missense	Exon 8 of 9	ENSP00000299206.4	Q9UGP5-1
	POLL	ENST00000370169.5	TSL:1	c.1325G>C	p.Gly442Ala	missense	Exon 7 of 8	ENSP00000359188.1	Q9UGP5-1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251196 AF XY: 0.0000221

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461656 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727132

African (AFR) AF: 0.000209 AC: 7 AN: 33478

American (AMR) AF: 0.0000895 AC: 4 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111958

Other (OTH) AF: 0.0000994 AC: 6 AN: 60392

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152344 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74488

African (AFR) AF: 0.000433 AC: 18 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000900 Hom.: 0

Bravo AF: 0.000159

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.19	T
Polyphen		0.98	D
Vest4		0.78
MVP		0.70
MPC		0.71
ClinPred		0.83	D
GERP RS		5.6
Varity_R		0.85
gMVP		0.71
Mutation Taster		=149/151	disease causing

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: rs149081648; hg19: chr10-103340043;