Variant 6-30949214-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080870.4(MUCL3):c.750A>C(p.Glu250Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000572 in 1,398,548 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: not found (cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

MUCL3
NM_080870.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.769

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046123087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUCL3	NM_080870.4 linkuse as main transcript	c.750A>C	p.Glu250Asp	missense_variant	2/3	ENST00000462446.6
HCG21	NR_138040.1 linkuse as main transcript	n.257-2636T>G		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.750A>C	p.Glu250Asp	missense_variant	2/3	5	NM_080870.4	A2
HCG21	ENST00000419481.1 linkuse as main transcript	n.225-2855T>G		intron_variant, non_coding_transcript_variant		3
MUCL3	ENST00000636043.1 linkuse as main transcript	c.951A>C	p.Glu317Asp	missense_variant	5/6	5		P4
SFTA2	ENST00000634371.1 linkuse as main transcript	c.-9+3148T>G		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000651

AC:

AN:

153718

Hom.:

AF XY:

0.0000123

AC XY:

AN XY:

81510

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:

0.00

Gnomad NFE exome

AF:

0.0000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000572

AC:

AN:

1398548

Hom.:

Cov.:

AF XY:

0.00000725

AC XY:

AN XY:

689752

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000742

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

Apr 28, 2022

The c.750A>C (p.E250D) alteration is located in exon 2 (coding exon 2) of the DPCR1 gene. This alteration results from a A to C substitution at nucleotide position 750, causing the glutamic acid (E) at amino acid position 250 to be replaced by an aspartic acid (D). 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

0.087

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

Cadd

Benign

0.29

Dann

Uncertain

0.98

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.40

T;T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.046

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.20

Polyphen

0.039

.;B;.

Vest4

0.053, 0.016

MutPred

0.10

.;Loss of methylation at K248 (P = 0.0958);Loss of methylation at K248 (P = 0.0958);

MVP

0.030

MPC

0.55

ClinPred

0.088

GERP RS

-3.7

Varity_R

0.026

gMVP

0.071

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