NM_015332.4:c.642+441A>C

Variant names:

• chr7-44427130-T-G
• rs2240100
• NM_015332.4:c.642+441A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NUDCD3	NM_015332.4	c.642+441A>C		intron_variant	Intron 3 of 5	ENST00000355451.8	NP_056147.2
NUDCD3	XM_011515247.3	c.642+441A>C		intron_variant	Intron 3 of 5		XP_011513549.1
NUDCD3	XM_017011908.2	c.642+441A>C		intron_variant	Intron 3 of 3		XP_016867397.1
NUDCD3	XR_007059994.1	n.700+441A>C		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUDCD3	ENST00000355451.8	c.642+441A>C		intron_variant	Intron 3 of 5	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

African (AFR) AF: 0.271 AC: 11255 AN: 41478

American (AMR) AF: 0.504 AC: 7705 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1084 AN: 3466

East Asian (EAS) AF: 0.522 AC: 2688 AN: 5146

South Asian (SAS) AF: 0.461 AC: 2222 AN: 4818

European-Finnish (FIN) AF: 0.430 AC: 4549 AN: 10568

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.411 AC: 27925 AN: 67968

Other (OTH) AF: 0.405 AC: 852 AN: 2106

Alfa AF: 0.405 Hom.: 56647

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
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2240100; hg19: chr7-44466729;