19-45349272-C-T

Variant names:

• chr19-45349272-C-T
• rs10853773
• NM_177417.3:c.970-157C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177417.3(KLC3):​c.970-157C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,824 control chromosomes in the GnomAD database, including 12,544 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 0.37 (12544 hom., cov: 31)
• Consequence: KLC3 NM_177417.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 8 publications found

Genes affected

KLC3 (HGNC:20717): (kinesin light chain 3) This gene encodes a member of the kinesin light chain gene family. Kinesins are molecular motors involved in the transport of cargo along microtubules, and are composed of two kinesin heavy chain (KHC) and two kinesin light chain (KLC) molecules. KLCs are thought to typically be involved in binding cargo and regulating kinesin activity. In the rat, a protein similar to this gene product is expressed in post-meiotic spermatids, where it associates with structural components of sperm tails and mitochondria. [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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLC3	NM_177417.3	c.970-157C>T		intron_variant	Intron 7 of 12	ENST00000391946.7	NP_803136.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLC3	ENST00000391946.7	c.970-157C>T		intron_variant	Intron 7 of 12	1	NM_177417.3	ENSP00000375810.2
KLC3	ENST00000470402.1	c.1012-157C>T		intron_variant	Intron 6 of 11	1		ENSP00000436019.1
KLC3	ENST00000585434.5	c.967-157C>T		intron_variant	Intron 7 of 12	1		ENSP00000466067.1
KLC3	ENST00000589373.5	c.970-157C>T		intron_variant	Intron 8 of 9	5		ENSP00000465950.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56679 AN: 151706 Hom.: 12517 Cov.: 31

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.374 AC: 56769 AN: 151824 Hom.: 12544 Cov.: 31 AF XY: 0.368 AC XY: 27334 AN XY: 74194

African (AFR) AF: 0.624 AC: 25802 AN: 41356

American (AMR) AF: 0.313 AC: 4779 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3472

East Asian (EAS) AF: 0.363 AC: 1873 AN: 5154

South Asian (SAS) AF: 0.221 AC: 1063 AN: 4808

European-Finnish (FIN) AF: 0.273 AC: 2877 AN: 10550

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18450 AN: 67916

Other (OTH) AF: 0.309 AC: 652 AN: 2108

Alfa AF: 0.316 Hom.: 16083

Bravo AF: 0.395

Asia WGS AF: 0.338 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		-0.095
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10853773; hg19: chr19-45852530;