6-30941073-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080870.4(MUCL3):c.74G>C(p.Trp25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000071 in 1,550,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: MUCL3 NM_080870.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0610

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]

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12487075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUCL3	NM_080870.4	c.74G>C	p.Trp25Ser	missense_variant	1/3	ENST00000462446.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUCL3	ENST00000462446.6	c.74G>C	p.Trp25Ser	missense_variant	1/3	5	NM_080870.4	A2
MUCL3	ENST00000636043.1	c.275G>C	p.Trp92Ser	missense_variant	4/6	5		P4
SFTA2	ENST00000634371.1	c.-8-9278C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.000478

GnomAD3 exomes AF: 0.0000786 AC: 12 AN: 152692 Hom.: 0 AF XY: 0.0000616 AC XY: 5 AN XY: 81162

Gnomad AFR exome AF: 0.000254

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000504

Gnomad OTH exome AF: 0.000231

GnomAD4 exome AF: 0.0000601 AC: 84 AN: 1397872 Hom.: 0 Cov.: 31 AF XY: 0.0000580 AC XY: 40 AN XY: 689540

Gnomad4 AFR exome AF: 0.000760

Gnomad4 AMR exome AF: 0.000140

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: 0.0000371

Gnomad4 OTH exome AF: 0.000172

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74356

Gnomad4 AFR AF: 0.000483

Gnomad4 AMR AF: 0.000262

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: 0.000478

Alfa AF: 0.0000285 Hom.: 0

Bravo AF: 0.000159

ExAC AF: 0.0000373 AC: 1

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

Sep 16, 2021

The c.74G>C (p.W25S) alteration is located in exon 1 (coding exon 1) of the DPCR1 gene. This alteration results from a G to C substitution at nucleotide position 74, causing the tryptophan (W) at amino acid position 25 to be replaced by a serine (S). 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	0.22
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	16
Dann	Uncertain	0.98
DEOGEN2	Benign	0.035	T;T;T
Eigen	Benign	-0.058
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.44	T;T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	0.98	D;D
PrimateAI	Benign	0.26	T
Polyphen		0.99	.;D;.
Vest4		0.43, 0.42
MutPred		0.58		.;Gain of glycosylation at W25 (P = 0.0044);Gain of glycosylation at W25 (P = 0.0044);
MVP		0.48
MPC		1.5
ClinPred		0.22	T
GERP RS		2.2
Varity_R		0.096
gMVP		0.34

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: rs765315692; hg19: chr6-30908850;