NM_015332.4:c.307_309delGCAinsACG

Variant names:

• chr7-44485168-TGC-CGT
• NM_015332.4:c.307_309delGCAinsACG
• NUDCD3 p.Ala103Thr

Variant summary

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

The NM_015332.4(NUDCD3):​c.307_309delGCAinsACG​(p.Ala103Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A103V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUDCD3 NM_015332.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502
• Publications: 0 publications found

Genes affected

NUDCD3 (HGNC:22208): (NudC domain containing 3) The product of this gene functions to maintain the stability of dynein intermediate chain. Depletion of this gene product results in aggregation and degradation of dynein intermediate chain, mislocalization of the dynein complex from kinetochores, spindle microtubules, and spindle poles, and loss of gamma-tubulin from spindle poles. The protein localizes to the Golgi apparatus during interphase, and levels of the protein increase after the G1/S transition. [provided by RefSeq, Jul 2008]

NUDCD3 Gene-Disease associations (from GenCC):

• severe combined immunodeficiency

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015332.4. 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
	NUDCD3	NM_015332.4	MANE Select	c.307_309delGCAinsACG	p.Ala103Thr	missense	N/A	NP_056147.2	Q8IVD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDCD3	ENST00000355451.8	TSL:1 MANE Select	c.307_309delGCAinsACG	p.Ala103Thr	missense	N/A	ENSP00000347626.6	Q8IVD9
	NUDCD3	ENST00000873879.1		c.307_309delGCAinsACG	p.Ala103Thr	missense	N/A	ENSP00000543938.1
	NUDCD3	ENST00000962334.1		c.307_309delGCAinsACG	p.Ala103Thr	missense	N/A	ENSP00000632393.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.50

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-44524767;