6-30949470-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_080870.4(MUCL3):c.1006G>A(p.Ala336Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000858 in 106,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00035 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUCL3
NM_080870.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0810

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00892216).

BP6

Variant 6-30949470-G-A is Benign according to our data. Variant chr6-30949470-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3150720.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUCL3	NM_080870.4 linkuse as main transcript	c.1006G>A	p.Ala336Thr	missense_variant	2/3	ENST00000462446.6
HCG21	NR_138040.1 linkuse as main transcript	n.256+2892C>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.1006G>A	p.Ala336Thr	missense_variant	2/3	5	NM_080870.4	A2
HCG21	ENST00000419481.1 linkuse as main transcript	n.225-3111C>T		intron_variant, non_coding_transcript_variant		3
MUCL3	ENST00000636043.1 linkuse as main transcript	c.1207G>A	p.Ala403Thr	missense_variant	5/6	5		P4
SFTA2	ENST00000634371.1 linkuse as main transcript	c.-9+2892C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000859

AC:

AN:

105944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000971

Gnomad AMI

AF:

0.00137

Gnomad AMR

AF:

0.00119

Gnomad ASJ

AF:

0.000743

Gnomad EAS

AF:

0.00276

Gnomad SAS

AF:

0.00254

Gnomad FIN

AF:

0.000652

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000537

Gnomad OTH

AF:

0.000730

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000347

AC:

441

AN:

1271446

Hom.:

Cov.:

164

AF XY:

0.000364

AC XY:

227

AN XY:

623482

show subpopulations

Gnomad4 AFR exome

AF:

0.000406

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.000193

Gnomad4 EAS exome

AF:

0.000955

Gnomad4 SAS exome

AF:

0.00222

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000162

Gnomad4 OTH exome

AF:

0.000753

GnomAD4 genome

AF:

0.000858

AC:

AN:

106038

Hom.:

Cov.:

AF XY:

0.000827

AC XY:

AN XY:

50816

show subpopulations

Gnomad4 AFR

AF:

0.000968

Gnomad4 AMR

AF:

0.00119

Gnomad4 ASJ

AF:

0.000743

Gnomad4 EAS

AF:

0.00276

Gnomad4 SAS

AF:

0.00254

Gnomad4 FIN

AF:

0.000652

Gnomad4 NFE

AF:

0.000537

Gnomad4 OTH

AF:

0.000720

Alfa

AF:

0.00122

Hom.:

ExAC

AF:

0.000153

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

Cadd

Benign

0.15

Dann

Benign

0.36

DEOGEN2

Benign

0.0032

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.000060

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.0089

T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

Polyphen

0.0090

.;B

Vest4

0.024

MVP

0.014

MPC

0.48

ClinPred

0.0025

GERP RS

1.1

gMVP

0.044

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