Variant rs2240804 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080870.4(MUCL3):c.4178G>A(p.Arg1393Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,778 control chromosomes in the GnomAD database, including 87,566 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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: 𝑓 0.26 ( 6222 hom., cov: 33)

Exomes 𝑓: 0.33 ( 81344 hom. )

Consequence

MUCL3
NM_080870.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.183

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034334064).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUCL3	NM_080870.4 linkuse as main transcript	c.4178G>A	p.Arg1393Gln	missense_variant	3/3	ENST00000462446.6
HCG21	NR_138040.1 linkuse as main transcript	n.87-582C>T		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.4178G>A	p.Arg1393Gln	missense_variant	3/3	5	NM_080870.4	A2
HCG21	ENST00000419481.1 linkuse as main transcript	n.178C>T		non_coding_transcript_exon_variant	2/3	3
MUCL3	ENST00000636043.1 linkuse as main transcript	c.4379G>A	p.Arg1460Gln	missense_variant	6/6	5		P4
SFTA2	ENST00000634371.1 linkuse as main transcript	c.-234C>T		5_prime_UTR_variant	3/6	5

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39266

AN:

152100

Hom.:

6227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0815

Gnomad AMI

AF:

0.303

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.255

GnomAD3 exomes

AF:

0.294

AC:

73813

AN:

250770

Hom.:

12063

AF XY:

0.301

AC XY:

40811

AN XY:

135504

show subpopulations

Gnomad AFR exome

AF:

0.0755

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.184

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.391

Gnomad NFE exome

AF:

0.362

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.327

AC:

477577

AN:

1461562

Hom.:

81344

Cov.:

AF XY:

0.326

AC XY:

236796

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.0713

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.364

Gnomad4 EAS exome

AF:

0.188

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.384

Gnomad4 NFE exome

AF:

0.350

Gnomad4 OTH exome

AF:

0.296

GnomAD4 genome

AF:

0.258

AC:

39266

AN:

152216

Hom.:

6222

Cov.:

AF XY:

0.258

AC XY:

19176

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0816

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.395

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.213

Gnomad4 FIN

AF:

0.391

Gnomad4 NFE

AF:

0.354

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.335

Hom.:

10120

Bravo

AF:

0.239

TwinsUK

AF:

0.348

AC:

1290

ALSPAC

AF:

0.357

AC:

1375

ESP6500AA

AF:

0.0976

AC:

430

ESP6500EA

AF:

0.362

AC:

3114

ExAC

AF:

0.297

AC:

36121

Asia WGS

AF:

0.152

AC:

534

AN:

3478

EpiCase

AF:

0.359

EpiControl

AF:

0.361

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.60

T;T;T

MetaRNN

Benign

0.0034

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.23

Polyphen

0.35

.;B;.

Vest4

0.056, 0.021

MPC

0.57

ClinPred

0.027

GERP RS

-1.6

Varity_R

0.044

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over