chr11-74634505-T-C

Variant names:

• chr11-74634505-T-C
• rs3824999
• NM_006591.3:c.1007-78T>C

Variant summary

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

The NM_006591.3(POLD3):​c.1007-78T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: POLD3 NM_006591.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 0 publications found

Genes affected

POLD3 (HGNC:20932): (DNA polymerase delta 3, accessory subunit) This gene encodes the 66-kDa subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. The encoded protein plays a role in regulating the activity of DNA polymerase delta through interactions with other subunits and the processivity cofactor proliferating cell nuclear antigen (PCNA). Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Mar 2012]

POLD3 Gene-Disease associations (from GenCC):

• hearing loss disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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 (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006591.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLD3	NM_006591.3	MANE Select	c.1007-78T>C		intron	N/A	NP_006582.1
	POLD3	NM_001363597.2		c.890-78T>C		intron	N/A	NP_001350526.1
	POLD3	NR_046409.2		n.981-78T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLD3	ENST00000263681.7	TSL:1 MANE Select	c.1007-78T>C		intron	N/A	ENSP00000263681.2
	POLD3	ENST00000527458.5	TSL:1	c.890-78T>C		intron	N/A	ENSP00000432951.1
	POLD3	ENST00000532497.5	TSL:1	c.689-78T>C		intron	N/A	ENSP00000436018.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.63
PhyloP100		0.074

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: rs3824999; hg19: chr11-74345550;