10-101579789-T-G

Variant names:

• chr10-101579789-T-G
• rs1389922478
• NM_001174084.2:c.1392A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001174084.2(POLL):​c.1392A>C​(p.Gln464His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: POLL NM_001174084.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.331
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041303724).

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.1392A>C	p.Gln464His	missense	Exon 9 of 9	NP_001167555.1	Q9UGP5-1
	POLL	NM_013274.4		c.1392A>C	p.Gln464His	missense	Exon 9 of 9	NP_037406.1	Q9UGP5-1
	POLL	NM_001174085.2		c.1116A>C	p.Gln372His	missense	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.1392A>C	p.Gln464His	missense	Exon 9 of 9	ENSP00000359181.3	Q9UGP5-1
	POLL	ENST00000299206.8	TSL:1	c.1392A>C	p.Gln464His	missense	Exon 9 of 9	ENSP00000299206.4	Q9UGP5-1
	POLL	ENST00000370169.5	TSL:1	c.1392A>C	p.Gln464His	missense	Exon 8 of 8	ENSP00000359188.1	Q9UGP5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000800 AC: 2 AN: 249868 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461310 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726922

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53100

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

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111854

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.8
DANN	Benign	0.83
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.41	N
PhyloP100		-0.33
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.026
Sift	Benign	0.30	T
Sift4G	Benign	0.23	T
Polyphen		0.0030	B
Vest4		0.13
MutPred		0.29		Gain of loop (P = 0.069)
MVP		0.32
MPC		0.15
ClinPred		0.046	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.59
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1389922478; hg19: chr10-103339546;