rs2517449

chr6-30951924-T-Achr6-30951924-T-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.3460T>A(p.Leu1154Met) 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. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MUCL3 NM_080870.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.71

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=0.07865134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUCL3	NM_080870.4	c.3460T>A	p.Leu1154Met	missense_variant	2/3	ENST00000462446.6
HCG21	NR_138040.1	n.256+438A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUCL3	ENST00000462446.6	c.3460T>A	p.Leu1154Met	missense_variant	2/3	5	NM_080870.4	A2
HCG21	ENST00000419481.1	n.224+1143A>T		intron_variant, non_coding_transcript_variant		3
MUCL3	ENST00000636043.1	c.3661T>A	p.Leu1221Met	missense_variant	5/6	5		P4
SFTA2	ENST00000634371.1	c.-9+438A>T		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 97

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.2
Dann	Uncertain	0.98
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.17	T
Polyphen		1.0	.;D
Vest4		0.12
MutPred		0.15		.;Gain of MoRF binding (P = 0.0637);
MVP		0.11
MPC		1.3
ClinPred		0.24	T
GERP RS		-2.2
gMVP		0.025

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: rs2517449; hg19: chr6-30919701;