1-66826991-C-T

Variant names:

• chr1-66826991-C-T
• NM_024763.5:c.2168G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024763.5(DNAI4):​c.2168G>A​(p.Cys723Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAI4 NM_024763.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.70
• Publications: 0 publications found

Genes affected

DNAI4 (HGNC:26252): (dynein axonemal intermediate chain 4) Predicted to enable dynein heavy chain binding activity and dynein light chain binding activity. Predicted to be involved in axonemal dynein complex assembly and cilium movement. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in axoneme; dynein axonemal particle; and motile cilium. Predicted to be part of axonemal dynein complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000231080 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.922

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024763.5. 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
	DNAI4	NM_024763.5	MANE Select	c.2168G>A	p.Cys723Tyr	missense	Exon 15 of 17	NP_079039.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI4	ENST00000371026.8	TSL:1 MANE Select	c.2168G>A	p.Cys723Tyr	missense	Exon 15 of 17	ENSP00000360065.3	Q5VTH9-1
	DNAI4	ENST00000908566.1		c.2081G>A	p.Cys694Tyr	missense	Exon 14 of 16	ENSP00000578625.1
	DNAI4	ENST00000908565.1		c.2036G>A	p.Cys679Tyr	missense	Exon 14 of 16	ENSP00000578624.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		6.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-10	D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.71		Gain of sheet (P = 0.1539)
MVP		0.78
MPC		0.66
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.96
gMVP		0.87
Mutation Taster		=37/63	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr1-67292674;