6-30951924-T-G

Variant names:

• chr6-30951924-T-G
• rs2517449
• NM_080870.4:c.3460T>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>G​(p.Leu1154Val) 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: 0 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=0.072141945).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080870.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUCL3	NM_080870.4	MANE Select	c.3460T>G	p.Leu1154Val	missense	Exon 2 of 3	NP_543146.2
	HCG21	NR_138040.1		n.256+438A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUCL3	ENST00000462446.6	TSL:5 MANE Select	c.3460T>G	p.Leu1154Val	missense	Exon 2 of 3	ENSP00000417182.1
	HCG21	ENST00000419481.1	TSL:3	n.224+1143A>C		intron	N/A
	SFTA2	ENST00000634371.2	TSL:5	n.513+438A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 97

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.34
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0096	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.1	T
PhyloP100		-5.7
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.075
Sift4G	Benign	0.22	T
Polyphen		0.99	D
Vest4		0.041
MutPred		0.12		Gain of methylation at K1150 (P = 0.0637)
MVP		0.12
MPC		0.62
ClinPred		0.12	T
GERP RS		-2.2
gMVP		0.026
Mutation Taster		=97/3	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;