chr6-30949363-C-A

Position:

• chr6-30949363-C-A

Variant summary

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

The NM_080870.4(MUCL3):​c.899C>A​(p.Ser300Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: MUCL3 NM_080870.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.810

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 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=0.13948867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUCL3	NM_080870.4	c.899C>A	p.Ser300Tyr	missense_variant	2/3	ENST00000462446.6
HCG21	NR_138040.1	n.257-2785G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUCL3	ENST00000462446.6	c.899C>A	p.Ser300Tyr	missense_variant	2/3	5	NM_080870.4	A2
HCG21	ENST00000419481.1	n.225-3004G>T		intron_variant, non_coding_transcript_variant		3
MUCL3	ENST00000636043.1	c.1100C>A	p.Ser367Tyr	missense_variant	5/6	5		P4
SFTA2	ENST00000634371.1	c.-9+2999G>T		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 16, 2021

The c.899C>A (p.S300Y) alteration is located in exon 2 (coding exon 2) of the DPCR1 gene. This alteration results from a C to A substitution at nucleotide position 899, causing the serine (S) at amino acid position 300 to be replaced by a tyrosine (Y). 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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.47	T;T;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.3	.;N;.
REVEL	Benign	0.074
Sift4G	Uncertain	0.0090	.;D;D
Polyphen		0.98	.;D;.
Vest4		0.17, 0.17
MutPred		0.13		.;Loss of glycosylation at S300 (P = 0.0223);Loss of glycosylation at S300 (P = 0.0223);
MVP		0.34
MPC		0.64
ClinPred		0.24	T
GERP RS		0.78
Varity_R		0.031
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-30917140;