1-85066028-C-T

Position:

• chr1-85066028-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145172.5(DNAI3):​c.-15+3542C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,212 control chromosomes in the GnomAD database, including 56,490 homozygotes. 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 0.86 (56490 hom., cov: 32)
• Consequence: DNAI3 NM_145172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676

Genes affected

DNAI3 (HGNC:30711): (dynein axonemal intermediate chain 3) Enables Arp2/3 complex binding activity. Involved in negative regulation of Arp2/3 complex-mediated actin nucleation and negative regulation of cell migration. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAI3	NM_145172.5	c.-15+3542C>T		intron_variant		ENST00000294664.11
DNAI3	NM_001288563.2	c.-15+3542C>T		intron_variant
DNAI3	XM_047444741.1	c.-15+3542C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAI3	ENST00000294664.11	c.-15+3542C>T		intron_variant		1	NM_145172.5	P2

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130809 AN: 152094 Hom.: 56439 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.860 AC: 130914 AN: 152212 Hom.: 56490 Cov.: 32 AF XY: 0.863 AC XY: 64202 AN XY: 74430

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.899

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.883

Gnomad4 OTH AF: 0.852

Alfa AF: 0.877 Hom.: 112580

Bravo AF: 0.856

Asia WGS AF: 0.845 AC: 2939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs6695223; hg19: chr1-85531711;