Variant chr5-119121010-C-G 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_001290321.3(DMXL1):c.973C>G(p.Leu325Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DMXL1
NM_001290321.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.446

Variant links:

Genes affected

DMXL1 (HGNC:2937): (Dmx like 1) The protein encoded by this gene is a member of the WD repeat superfamily of proteins, which have regulatory functions. This gene is expressed in many tissue types including several types of eye tissue, and it has been associated with ocular phenotypes. In addition, it is upregulated in cultured cells that overexpress growth factor independence 1B, a transcription factor that is essential for hematopoietic cell development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

DMXL1 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=0.06982738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMXL1	NM_001290321.3 linkuse as main transcript	c.973C>G	p.Leu325Val	missense_variant	9/44	ENST00000539542.6	NP_001277250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DMXL1	ENST00000539542.6 linkuse as main transcript	c.973C>G	p.Leu325Val	missense_variant	9/44	1	NM_001290321.3	ENSP00000439479	A1
DMXL1	ENST00000311085.8 linkuse as main transcript	c.973C>G	p.Leu325Val	missense_variant	9/43	1		ENSP00000309690	P3
DMXL1	ENST00000503802.5 linkuse as main transcript	c.973C>G	p.Leu325Val	missense_variant	10/13	1		ENSP00000427692
DMXL1	ENST00000514151.1 linkuse as main transcript	n.455C>G		non_coding_transcript_exon_variant	5/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 24, 2022

The c.973C>G (p.L325V) alteration is located in exon 9 (coding exon 9) of the DMXL1 gene. This alteration results from a C to G substitution at nucleotide position 973, causing the leucine (L) at amino acid position 325 to be replaced by a valine (V). 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

0.074

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0050

T;T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;.;L

MutationTaster

Benign

0.77

D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.17

N;N;N

REVEL

Benign

0.069

Sift

Benign

0.37

T;T;T

Sift4G

Benign

0.17

T;.;.

Polyphen

0.051, 0.014

.;B;B

Vest4

0.36, 0.37

MutPred

0.24

Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);

MVP

0.28

MPC

0.057

ClinPred

0.12

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.038

gMVP

0.38

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over