7-44427130-T-G

Position:

• chr7-44427130-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015332.4(NUDCD3):​c.642+441A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,036 control chromosomes in the GnomAD database, including 11,877 homozygotes. 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 0.39 (11877 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]

NUDCD3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDCD3	NM_015332.4	c.642+441A>C		intron_variant		ENST00000355451.8	NP_056147.2
NUDCD3	XM_011515247.3	c.642+441A>C		intron_variant			XP_011513549.1
NUDCD3	XM_017011908.2	c.642+441A>C		intron_variant			XP_016867397.1
NUDCD3	XR_007059994.1	n.700+441A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDCD3	ENST00000355451.8	c.642+441A>C		intron_variant		1	NM_015332.4	ENSP00000347626.6

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58825 AN: 151918 Hom.: 11864 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.387 AC: 58849 AN: 152036 Hom.: 11877 Cov.: 32 AF XY: 0.393 AC XY: 29187 AN XY: 74300

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.405

Alfa AF: 0.404 Hom.: 26664

Bravo AF: 0.388

Asia WGS AF: 0.499 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.74

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;