Variant 6-30948850-G-T 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_080870.4(MUCL3):c.386G>T(p.Gly129Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,551,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

MUCL3
NM_080870.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.280

Variant links:

Genes affected

MUCL3 (HGNC:21666): (mucin like 3) Predicted to be located in cytoplasm and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MUCL3 links:

HCG21 (HGNC:31335): (HLA complex group 21)

HCG21 links:

SFTA2 (HGNC:18386): (surfactant associated 2) Predicted to be located in Golgi apparatus; extracellular region; and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

SFTA2 links:

Genome browser will be placed here

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=0.07199091).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUCL3	NM_080870.4 linkuse as main transcript	c.386G>T	p.Gly129Val	missense_variant	2/3	ENST00000462446.6
HCG21	NR_138040.1 linkuse as main transcript	n.257-2272C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MUCL3	ENST00000462446.6 linkuse as main transcript	c.386G>T	p.Gly129Val	missense_variant	2/3	5	NM_080870.4	A2
HCG21	ENST00000419481.1 linkuse as main transcript	n.225-2491C>A		intron_variant, non_coding_transcript_variant		3
MUCL3	ENST00000636043.1 linkuse as main transcript	c.587G>T	p.Gly196Val	missense_variant	5/6	5		P4
SFTA2	ENST00000634371.1 linkuse as main transcript	c.-9+3512C>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000137

AC:

AN:

153690

Hom.:

AF XY:

0.000135

AC XY:

AN XY:

81554

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:

0.000131

Gnomad NFE exome

AF:

0.000320

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000304

AC:

425

AN:

1399366

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

214

AN XY:

690192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000812

Gnomad4 NFE exome

AF:

0.000385

Gnomad4 OTH exome

AF:

0.0000862

GnomAD4 genome

AF:

0.000197

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000295

Hom.:

Bravo

AF:

0.000174

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000173

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

Aug 02, 2021

The c.386G>T (p.G129V) alteration is located in exon 2 (coding exon 2) of the DPCR1 gene. This alteration results from a G to T substitution at nucleotide position 386, causing the glycine (G) at amino acid position 129 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

0.18

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.39

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.026

T;T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.92

N;N

PrimateAI

Benign

0.23

Polyphen

1.0

.;D;.

Vest4

0.28, 0.16

MVP

0.29

MPC

1.6

ClinPred

0.23

GERP RS

2.5

Varity_R

0.038

gMVP

0.078

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