1-85066028-C-T

Variant names:

• chr1-85066028-C-T
• rs6695223
• NM_145172.5:c.-15+3542C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145172.5. 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
	DNAI3	NM_145172.5	MANE Select	c.-15+3542C>T		intron	N/A	NP_660155.2
	DNAI3	NM_001288563.2		c.-15+3542C>T		intron	N/A	NP_001275492.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI3	ENST00000294664.11	TSL:1 MANE Select	c.-15+3542C>T		intron	N/A	ENSP00000294664.6
	DNAI3	ENST00000964695.1		c.-14-5900C>T		intron	N/A	ENSP00000634754.1
	DNAI3	ENST00000326813.12	TSL:2	c.-15+3542C>T		intron	N/A	ENSP00000317463.8

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

African (AFR) AF: 0.794 AC: 32978 AN: 41518

American (AMR) AF: 0.899 AC: 13748 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2934 AN: 3472

East Asian (EAS) AF: 0.799 AC: 4125 AN: 5164

South Asian (SAS) AF: 0.920 AC: 4435 AN: 4820

European-Finnish (FIN) AF: 0.914 AC: 9691 AN: 10604

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60076 AN: 68026

Other (OTH) AF: 0.852 AC: 1800 AN: 2112

Alfa AF: 0.875 Hom.: 240038

Bravo AF: 0.856

Asia WGS AF: 0.845 AC: 2939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.73
PhyloP100		0.68
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: rs6695223; hg19: chr1-85531711;