6-158641347-A-G

Variant names:

• chr6-158641347-A-G
• rs751496503
• NM_006519.4:c.41T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006519.4(DYNLT1):​c.41T>C​(p.Val14Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,756 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V14G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DYNLT1 NM_006519.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.80
• Publications: 0 publications found

Genes affected

DYNLT1 (HGNC:11697): (dynein light chain Tctex-type 1) This gene encodes a component of the motor complex, cytoplasmic dynein, which transports cellular cargo along microtubules in the cell. The encoded protein regulates the length of primary cilia which are sensory organelles found on the surface of cells. The protein encoded by this gene interacts with viral proteins, like the minor capsid protein L2 of human papillomavirus, and is required for dynein-mediated delivery of the viral nucleic acid to the host nucleus. This protein interacts with oncogenic nucleoporins to disrupt gene regulation and cause leukemic transformation. Pseudogenes of this gene are present on chromosomes 4 and 17. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006519.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT1	NM_006519.4	MANE Select	c.41T>C	p.Val14Ala	missense	Exon 2 of 5	NP_006510.1	P63172
	DYNLT1	NM_001291603.2		c.41T>C	p.Val14Ala	missense	Exon 2 of 5	NP_001278532.1
	DYNLT1	NM_001291602.2		c.27+3335T>C		intron	N/A	NP_001278531.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNLT1	ENST00000367089.8	TSL:1 MANE Select	c.41T>C	p.Val14Ala	missense	Exon 2 of 5	ENSP00000356056.3	P63172
	DYNLT1	ENST00000883048.1		c.27+3335T>C		intron	N/A	ENSP00000553107.1
	DYNLT1	ENST00000367085.3	TSL:2	n.71T>C		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446756 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 719228

African (AFR) AF: 0.00 AC: 0 AN: 32638

American (AMR) AF: 0.00 AC: 0 AN: 40372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25752

East Asian (EAS) AF: 0.00 AC: 0 AN: 39024

South Asian (SAS) AF: 0.00 AC: 0 AN: 82882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53214

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5734

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107332

Other (OTH) AF: 0.00 AC: 0 AN: 59808

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.075
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		8.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.24
Sift	Benign	1.0	T
Sift4G	Benign	0.93	T
Polyphen		0.0060	B
Vest4		0.60
MutPred		0.56		Gain of disorder (P = 0.0745)
MVP		0.73
MPC		0.057
ClinPred		0.85	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.59
Mutation Taster		=165/135	polymorphism

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: rs751496503; hg19: chr6-159062379;