Variant 6-30948868-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_080870.4(MUCL3):c.404G>A(p.Arg135Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 1,551,512 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R135W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0098 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 30 hom. )

Consequence

MUCL3
NM_080870.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.182

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025999844).

BP6

Variant 6-30948868-G-A is Benign according to our data. Variant chr6-30948868-G-A is described in ClinVar as [Benign]. Clinvar id is 770548.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00982 (1495/152252) while in subpopulation AFR AF= 0.0241 (1002/41536). AF 95% confidence interval is 0.0229. There are 22 homozygotes in gnomad4. There are 715 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUCL3	NM_080870.4 linkuse as main transcript	c.404G>A	p.Arg135Gln	missense_variant	2/3	ENST00000462446.6
HCG21	NR_138040.1 linkuse as main transcript	n.257-2290C>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.404G>A	p.Arg135Gln	missense_variant	2/3	5	NM_080870.4	A2
HCG21	ENST00000419481.1 linkuse as main transcript	n.225-2509C>T		intron_variant, non_coding_transcript_variant		3
MUCL3	ENST00000636043.1 linkuse as main transcript	c.605G>A	p.Arg202Gln	missense_variant	5/6	5		P4
SFTA2	ENST00000634371.1 linkuse as main transcript	c.-9+3494C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00985

AC:

1498

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00976

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00787

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00583

AC:

895

AN:

153424

Hom.:

AF XY:

0.00570

AC XY:

464

AN XY:

81430

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.00569

Gnomad ASJ exome

AF:

0.0142

Gnomad EAS exome

AF:

0.00603

Gnomad SAS exome

AF:

0.00810

Gnomad FIN exome

AF:

0.00118

Gnomad NFE exome

AF:

0.00257

Gnomad OTH exome

AF:

0.00811

GnomAD4 exome

AF:

0.00336

AC:

4706

AN:

1399260

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

2427

AN XY:

690166

show subpopulations

Gnomad4 AFR exome

AF:

0.0187

Gnomad4 AMR exome

AF:

0.00670

Gnomad4 ASJ exome

AF:

0.0156

Gnomad4 EAS exome

AF:

0.00319

Gnomad4 SAS exome

AF:

0.00943

Gnomad4 FIN exome

AF:

0.000731

Gnomad4 NFE exome

AF:

0.00196

Gnomad4 OTH exome

AF:

0.00667

GnomAD4 genome

AF:

0.00982

AC:

1495

AN:

152252

Hom.:

Cov.:

AF XY:

0.00960

AC XY:

715

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0241

Gnomad4 AMR

AF:

0.00974

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00789

Gnomad4 SAS

AF:

0.00954

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00402

Hom.:

Bravo

AF:

0.0112

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ExAC

AF:

0.00794

AC:

184

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.2

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0089

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.59

T;T;T

MetaRNN

Benign

0.0026

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.52

.;N;.

REVEL

Benign

0.029

Sift4G

Benign

0.43

.;T;T

Polyphen

0.44

.;B;.

Vest4

0.085, 0.034

MVP

0.055

MPC

0.65

ClinPred

0.0028

GERP RS

-1.6

Varity_R

0.030

gMVP

0.050

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