6-30953113-G-T

Variant names:

• chr6-30953113-G-T
• rs2240804
• NM_080870.4:c.4178G>T

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.4178G>T​(p.Arg1393Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MUCL3 NM_080870.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• 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=0.14655057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUCL3	NM_080870.4	c.4178G>T	p.Arg1393Leu	missense_variant	Exon 3 of 3	ENST00000462446.6	NP_543146.2
HCG21	NR_138040.1	n.87-582C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUCL3	ENST00000462446.6	c.4178G>T	p.Arg1393Leu	missense_variant	Exon 3 of 3	5	NM_080870.4	ENSP00000417182.1
HCG21	ENST00000419481.1	n.178C>A		non_coding_transcript_exon_variant	Exon 2 of 3	3
SFTA2	ENST00000634371.2	n.288C>A		non_coding_transcript_exon_variant	Exon 3 of 6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461620 Hom.: 0 Cov.: 56 AF XY: 0.00000138 AC XY: 1 AN XY: 727114

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.18
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.9	.;N;.
REVEL	Benign	0.030
Sift4G	Pathogenic	0.0	.;D;D
Polyphen		0.97	.;D;.
Vest4		0.18, 0.22
MutPred		0.26		.;Gain of stability (P = 0.028);.;
MVP		0.19
MPC		0.68
ClinPred		0.70	D
GERP RS		-1.6
Varity_R		0.13
gMVP		0.43
Mutation Taster		=95/5	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: rs2240804; hg19: chr6-30920890;