rs2517449

Variant names:

• chr6-30951924-T-A
• rs2517449
• NM_080870.4:c.3460T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-30951924-T-A
• chr6-30951924-T-C
• chr6-30951924-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/20 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
• Publications: 27 publications found

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

Our verdict: Uncertain_significance. The variant received 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 rank	MANE	Protein	UniProt
MUCL3	NM_080870.4	c.3460T>A	p.Leu1154Met	missense_variant	Exon 2 of 3	ENST00000462446.6	NP_543146.2
HCG21	NR_138040.1	n.256+438A>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUCL3	ENST00000462446.6	c.3460T>A	p.Leu1154Met	missense_variant	Exon 2 of 3	5	NM_080870.4	ENSP00000417182.1
HCG21	ENST00000419481.1	n.224+1143A>T		intron_variant	Intron 2 of 2	3
SFTA2	ENST00000634371.2	n.513+438A>T		intron_variant	Intron 4 of 5	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
AlphaMissense	Benign	0.13
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
PhyloP100		-5.7
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-0.13	.;N
REVEL	Benign	0.061
Sift4G	Uncertain	0.057	.;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
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs2517449; hg19: chr6-30919701;