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GeneBe

6-30949185-G-A

Variant summary

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

The NM_080870.4(MUCL3):c.721G>A(p.Gly241Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000516 in 1,551,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

MUCL3
NM_080870.4 missense

Scores

14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.497
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]
HCG21 (HGNC:31335): (HLA complex group 21)
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]

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=0.03840065).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MUCL3NM_080870.4 linkuse as main transcriptc.721G>A p.Gly241Arg missense_variant 2/3 ENST00000462446.6
HCG21NR_138040.1 linkuse as main transcriptn.257-2607C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MUCL3ENST00000462446.6 linkuse as main transcriptc.721G>A p.Gly241Arg missense_variant 2/35 NM_080870.4 A2
HCG21ENST00000419481.1 linkuse as main transcriptn.225-2826C>T intron_variant, non_coding_transcript_variant 3
MUCL3ENST00000636043.1 linkuse as main transcriptc.922G>A p.Gly308Arg missense_variant 5/65 P4
SFTA2ENST00000634371.1 linkuse as main transcriptc.-9+3177C>T intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000651
AC:
1
AN:
153672
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
81518
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:
0.00000286
AC:
4
AN:
1399152
Hom.:
0
Cov.:
30
AF XY:
0.00000290
AC XY:
2
AN XY:
690080
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:
0.00
Gnomad4 NFE exome
AF:
9.27e-7
Gnomad4 OTH exome
AF:
0.0000345
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000340

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 submitterclinical testingAmbry GeneticsDec 09, 2023The c.721G>A (p.G241R) alteration is located in exon 2 (coding exon 2) of the DPCR1 gene. This alteration results from a G to A substitution at nucleotide position 721, causing the glycine (G) at amino acid position 241 to be replaced by an arginine (R). 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
0.13
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.76
Cadd
Benign
1.4
Dann
Benign
0.75
DEOGEN2
Benign
0.012
T;T;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0014
N
LIST_S2
Benign
0.54
T;T;T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.038
T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.18
T
Polyphen
0.018
.;B;.
Vest4
0.047, 0.044
MutPred
0.18
.;Gain of MoRF binding (P = 0.0244);Gain of MoRF binding (P = 0.0244);
MVP
0.030
MPC
0.70
ClinPred
0.050
T
GERP RS
-4.8
Varity_R
0.058
gMVP
0.053

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.

Other links and lift over

dbSNP: rs970231324; hg19: chr6-30916962; API