chr7-44390652-G-T

Position:

• chr7-44390652-G-T

Variant summary

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

The NM_015332.4(NUDCD3):​c.975+1645C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,130 control chromosomes in the GnomAD database, including 5,845 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 0.25 (5845 hom., cov: 32)
• Consequence: NUDCD3 NM_015332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDCD3	NM_015332.4	c.975+1645C>A		intron_variant		ENST00000355451.8	NP_056147.2
NUDCD3	XM_011515247.3	c.975+1645C>A		intron_variant			XP_011513549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDCD3	ENST00000355451.8	c.975+1645C>A		intron_variant		1	NM_015332.4	ENSP00000347626	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38022 AN: 152012 Hom.: 5847 Cov.: 32

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.250 AC: 38003 AN: 152130 Hom.: 5845 Cov.: 32 AF XY: 0.251 AC XY: 18643 AN XY: 74360

Gnomad4 AFR AF: 0.0633

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.256

Alfa AF: 0.313 Hom.: 13193

Bravo AF: 0.236

Asia WGS AF: 0.261 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.69

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: rs2331071; hg19: chr7-44430251;