7-95813378-TAAAAA-TAAAAAAAAAAA

Variant names:

• chr7-95813378-T-TAAAAAA
• rs35397709
• NM_001135556.2:c.314+51_314+56dupAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001135556.2(DYNC1I1):​c.314+51_314+56dupAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000032 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DYNC1I1 NM_001135556.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 0 publications found

Genes affected

DYNC1I1 (HGNC:2963): (dynein cytoplasmic 1 intermediate chain 1) Enables spectrin binding activity. Involved in vesicle transport along microtubule. Located in several cellular components, including kinetochore; recycling endosome; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135556.2. 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
	DYNC1I1	NM_001135556.2	MANE Select	c.314+51_314+56dupAAAAAA		intron	N/A	NP_001129028.1	O14576-2
	DYNC1I1	NM_004411.5		c.365+51_365+56dupAAAAAA		intron	N/A	NP_004402.1	O14576-1
	DYNC1I1	NM_001278421.2		c.365+51_365+56dupAAAAAA		intron	N/A	NP_001265350.1	O14576-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC1I1	ENST00000447467.6	TSL:1 MANE Select	c.314+41_314+42insAAAAAA		intron	N/A	ENSP00000392337.2	O14576-2
	DYNC1I1	ENST00000324972.10	TSL:1	c.365+41_365+42insAAAAAA		intron	N/A	ENSP00000320130.6	O14576-1
	DYNC1I1	ENST00000457059.2	TSL:1	c.314+41_314+42insAAAAAA		intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 141100 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000315 AC: 4 AN: 1267882 Hom.: 0 Cov.: 20 AF XY: 0.00000478 AC XY: 3 AN XY: 628200

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27076

American (AMR) AF: 0.00 AC: 0 AN: 24790

Ashkenazi Jewish (ASJ) AF: 0.0000481 AC: 1 AN: 20786

East Asian (EAS) AF: 0.00 AC: 0 AN: 35314

South Asian (SAS) AF: 0.0000293 AC: 2 AN: 68262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4900

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 992726

Other (OTH) AF: 0.00 AC: 0 AN: 52542

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 141100 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 68106

African (AFR) AF: 0.00 AC: 0 AN: 38740

American (AMR) AF: 0.00 AC: 0 AN: 14128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3312

East Asian (EAS) AF: 0.00 AC: 0 AN: 4838

South Asian (SAS) AF: 0.00 AC: 0 AN: 4424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64644

Other (OTH) AF: 0.00 AC: 0 AN: 1942

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35397709; hg19: chr7-95442690;