Variant 1-44806068-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001377534.1(DYNLT4):c.601T>C(p.Ser201Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000742 in 1,602,932 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

DYNLT4
NM_001377534.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNLT4	NM_001377534.1 linkuse as main transcript	c.601T>C	p.Ser201Pro	missense_variant	3/3	ENST00000339355.3	NP_001364463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNLT4	ENST00000339355.3 linkuse as main transcript	c.601T>C	p.Ser201Pro	missense_variant	3/3	6	NM_001377534.1	ENSP00000341803.2		Q5JR98
DYNLT4	ENST00000675259.1 linkuse as main transcript	c.601T>C	p.Ser201Pro	missense_variant	2/2			ENSP00000501642.1		Q5JR98

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000113

AC:

AN:

239542

Hom.:

AF XY:

0.0000916

AC XY:

AN XY:

131042

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000910

Gnomad ASJ exome

AF:

0.00178

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000652

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000738

AC:

107

AN:

1450712

Hom.:

Cov.:

AF XY:

0.0000680

AC XY:

AN XY:

720326

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000694

Gnomad4 ASJ exome

AF:

0.00206

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000586

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000289

Gnomad4 OTH exome

AF:

0.000234

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000167

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000908

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2022

The c.601T>C (p.S201P) alteration is located in exon 2 (coding exon 1) of the TCTEX1D4 gene. This alteration results from a T to C substitution at nucleotide position 601, causing the serine (S) at amino acid position 201 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.44

M_CAP

Benign

0.069

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.55

MutationAssessor

Pathogenic

3.5

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.43

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.89

MVP

0.23

ClinPred

0.93

GERP RS

4.3

Varity_R

0.78

gMVP

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over