Genetic Variant NM_001377534.1:c.290C>T (chr1-44806379-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001377534.1(DYNLT4):c.290C>T(p.Pro97Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000727 in 1,375,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Consequence

DYNLT4
NM_001377534.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

Publications

0 publications found

Variant links:

Genes affected

DYNLT4 (HGNC:32315): (dynein light chain Tctex-type 4) Enables protein phosphatase 1 binding activity. Predicted to be involved in microtubule-based movement. Located in acrosomal vesicle; cytoskeleton; and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

DYNLT4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16873598).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377534.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DYNLT4	NM_001377534.1	MANE Select	c.290C>T	p.Pro97Leu	missense	Exon 3 of 3	NP_001364463.1	Q5JR98
DYNLT4	NM_001013632.4		c.290C>T	p.Pro97Leu	missense	Exon 2 of 2	NP_001013654.1	Q5JR98
DYNLT4	NM_001377535.1		c.290C>T	p.Pro97Leu	missense	Exon 3 of 3	NP_001364464.1	Q5JR98

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DYNLT4	ENST00000339355.3	TSL:6 MANE Select	c.290C>T	p.Pro97Leu	missense	Exon 3 of 3	ENSP00000341803.2	Q5JR98
DYNLT4	ENST00000675259.1		c.290C>T	p.Pro97Leu	missense	Exon 2 of 2	ENSP00000501642.1	Q5JR98
DYNLT4	ENST00000854447.1		c.290C>T	p.Pro97Leu	missense	Exon 3 of 3	ENSP00000524506.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

125184

AF XY:

0.0000142

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000457

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000201

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000727

AC:

AN:

1375676

Hom.:

Cov.:

AF XY:

0.00000883

AC XY:

AN XY:

679830

show subpopulations

African (AFR)

AF:

0.0000346

AC:

AN:

28904

American (AMR)

AF:

0.0000303

AC:

AN:

33010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24398

East Asian (EAS)

AF:

0.00

AC:

AN:

34424

South Asian (SAS)

AF:

0.00

AC:

AN:

78068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4762

European-Non Finnish (NFE)

AF:

0.00000744

AC:

AN:

1075566

Other (OTH)

AF:

0.00

AC:

AN:

57074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.00000958

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

Eigen

Benign

0.14

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.65

M_CAP

Benign

0.018

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

3.3

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.047

Sift

Benign

0.070

Sift4G

Benign

0.31

Polyphen

0.84

Vest4

0.29

MutPred

0.36

Gain of MoRF binding (P = 0.0551)

MVP

0.26

ClinPred

0.89

GERP RS

5.4

Varity_R

0.14

gMVP

0.44

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over