rs2240100

chr7-44427130-T-Cchr7-44427130-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015332.4(NUDCD3):c.642+441A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,984 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
• Consequence: NUDCD3 NM_015332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUDCD3	NM_015332.4	c.642+441A>G		intron_variant		ENST00000355451.8
NUDCD3	XM_011515247.3	c.642+441A>G		intron_variant
NUDCD3	XM_017011908.2	c.642+441A>G		intron_variant
NUDCD3	XR_007059994.1	n.700+441A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDCD3	ENST00000355451.8	c.642+441A>G		intron_variant		1	NM_015332.4	P1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151984 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151984 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74210

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.3
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs2240100; hg19: chr7-44466729;