1-66827906-G-C

Position:

• chr1-66827906-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024763.5(DNAI4):​c.2018C>G​(p.Thr673Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAI4 NM_024763.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.44

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAI4	NM_024763.5	c.2018C>G	p.Thr673Arg	missense_variant	14/17	ENST00000371026.8	NP_079039.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI4	ENST00000371026.8	c.2018C>G	p.Thr673Arg	missense_variant	14/17	1	NM_024763.5	ENSP00000360065.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000415 AC: 6 AN: 1444964 Hom.: 0 Cov.: 27 AF XY: 0.00000556 AC XY: 4 AN XY: 719220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000453

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2023

The c.2018C>G (p.T673R) alteration is located in exon 14 (coding exon 14) of the WDR78 gene. This alteration results from a C to G substitution at nucleotide position 2018, causing the threonine (T) at amino acid position 673 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.18
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.012	D
Polyphen		0.98	D
Vest4		0.64
MutPred		0.41		Gain of solvent accessibility (P = 0.0808);
MVP		0.65
MPC		0.51
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.63
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-67293589;