6-30949404-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080870.4(MUCL3):c.940G>A(p.Glu314Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,347,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: MUCL3 NM_080870.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.54

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]

ACMG classification

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=0.05346486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUCL3	NM_080870.4	c.940G>A	p.Glu314Lys	missense_variant	2/3	ENST00000462446.6
HCG21	NR_138040.1	n.257-2826C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUCL3	ENST00000462446.6	c.940G>A	p.Glu314Lys	missense_variant	2/3	5	NM_080870.4	A2
HCG21	ENST00000419481.1	n.225-3045C>T		intron_variant, non_coding_transcript_variant		3
MUCL3	ENST00000636043.1	c.1141G>A	p.Glu381Lys	missense_variant	5/6	5		P4
SFTA2	ENST00000634371.1	c.-9+2958C>T		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000127 AC: 2 AN: 157240 Hom.: 0 AF XY: 0.0000120 AC XY: 1 AN XY: 83140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000405

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: 0.0000164

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 23 AN: 1347226 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 9 AN XY: 665216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000295

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: 0.0000201

Gnomad4 OTH exome AF: 0.0000184

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.940G>A (p.E314K) 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 940, causing the glutamic acid (E) at amino acid position 314 to be replaced by a lysine (K). 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	0.078
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.25
Dann	Benign	0.67
DEOGEN2	Benign	0.0071	T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00080	N
LIST_S2	Benign	0.49	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.053	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.20	T
Polyphen		0.039	.;B;.
Vest4		0.069, 0.048
MutPred		0.25		.;Gain of ubiquitination at E314 (P = 0.0016);Gain of ubiquitination at E314 (P = 0.0016);
MVP		0.067
MPC		0.56
ClinPred		0.014	T
GERP RS		-2.3
Varity_R		0.021
gMVP		0.45

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

Other links and lift over

dbSNP: rs747108138; hg19: chr6-30917181;