Variant chr1-66754731-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152665.3(DYNLT5):c.73A>C(p.Ser25Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

DYNLT5
NM_152665.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

Variant links:

Genes affected

DYNLT5 (HGNC:26882): (dynein light chain Tctex-type family member 5) Predicted to enable dynein intermediate chain binding activity. Predicted to be involved in microtubule-based movement. Predicted to be part of cytoplasmic dynein complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DYNLT5 links:

DYNLT5 (HGNC:):

DYNLT5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11329433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNLT5	NM_152665.3 linkuse as main transcript	c.73A>C	p.Ser25Arg	missense_variant	2/5	ENST00000282670.7	NP_689878.2	Q8N7M0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DYNLT5	ENST00000282670.7 linkuse as main transcript	c.73A>C	p.Ser25Arg	missense_variant	2/5	1	NM_152665.3	ENSP00000282670.2	Q8N7M0-1
DYNLT5	ENST00000528352.1 linkuse as main transcript	n.73A>C		non_coding_transcript_exon_variant	2/7	1		ENSP00000436731.1	E9PI84
DYNLT5	ENST00000491611.1 linkuse as main transcript	n.129A>C		non_coding_transcript_exon_variant	2/5	2
DYNLT5	ENST00000525663.5 linkuse as main transcript	n.202A>C		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250418

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135360

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Nov 15, 2024

The c.73A>C (p.S25R) alteration is located in exon 2 (coding exon 1) of the TCTEX1D1 gene. This alteration results from a A to C substitution at nucleotide position 73, causing the serine (S) at amino acid position 25 to be replaced by an arginine (R). 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

Benign

0.16

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.8

DANN

Benign

0.97

DEOGEN2

Benign

0.022

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.60

M_CAP

Benign

0.0045

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

REVEL

Benign

0.030

Sift

Uncertain

0.017

Sift4G

Benign

0.18

Polyphen

0.14

Vest4

0.27

MutPred

0.30

Gain of catalytic residue at S25 (P = 0.0019);

MVP

0.28

MPC

0.15

ClinPred

0.10

GERP RS

3.3

Varity_R

0.078

gMVP

0.18

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