chrX-24729032-A-C

Variant names:

• chrX-24729032-A-C
• rs929313
• NM_001330360.2:c.1686+1096A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001330360.2(POLA1):​c.1686+1096A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.52 (10997 hom., 16835 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: POLA1 NM_001330360.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 1 publications found

Genes affected

POLA1 (HGNC:9173): (DNA polymerase alpha 1, catalytic subunit) This gene encodes the catalytic subunit of DNA polymerase, which together with a regulatory and two primase subunits, forms the DNA polymerase alpha complex. The catalytic subunit plays an essential role in the initiation of DNA replication. [provided by RefSeq, Mar 2010]

POLA1 Gene-Disease associations (from GenCC):

• X-linked intellectual disability, van Esch type

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• X-linked reticulate pigmentary disorder

  Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLA1	NM_001330360.2	c.1686+1096A>C		intron_variant	Intron 15 of 36	ENST00000379068.8	NP_001317289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLA1	ENST00000379068.8	c.1686+1096A>C		intron_variant	Intron 15 of 36	5	NM_001330360.2	ENSP00000368358.3

Frequencies

GnomAD3 genomes AF: 0.515 AC: 57060 AN: 110757 Hom.: 11005 Cov.: 23

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.517

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.540

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.515 AC: 57080 AN: 110810 Hom.: 10997 Cov.: 23 AF XY: 0.509 AC XY: 16835 AN XY: 33052

African (AFR) AF: 0.319 AC: 9759 AN: 30569

American (AMR) AF: 0.610 AC: 6356 AN: 10415

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1401 AN: 2636

East Asian (EAS) AF: 0.664 AC: 2333 AN: 3513

South Asian (SAS) AF: 0.525 AC: 1372 AN: 2611

European-Finnish (FIN) AF: 0.576 AC: 3359 AN: 5829

Middle Eastern (MID) AF: 0.512 AC: 111 AN: 217

European-Non Finnish (NFE) AF: 0.593 AC: 31325 AN: 52826

Other (OTH) AF: 0.538 AC: 820 AN: 1523

Alfa AF: 0.564 Hom.: 66905

Bravo AF: 0.515

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.75
PhyloP100		0.0040
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: rs929313; hg19: chrX-24747149;