chr6-30953113-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080870.4(MUCL3):​c.4178G>A​(p.Arg1393Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,778 control chromosomes in the GnomAD database, including 87,566 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.26 (6222 hom., cov: 33)
  • Exomes 𝑓: 0.33 (81344 hom.)
• Consequence: MUCL3 NM_080870.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 42 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034334064).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUCL3	NM_080870.4	MANE Select	c.4178G>A	p.Arg1393Gln	missense	Exon 3 of 3	NP_543146.2
	HCG21	NR_138040.1		n.87-582C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUCL3	ENST00000462446.6	TSL:5 MANE Select	c.4178G>A	p.Arg1393Gln	missense	Exon 3 of 3	ENSP00000417182.1
	HCG21	ENST00000419481.1	TSL:3	n.178C>T		non_coding_transcript_exon	Exon 2 of 3
	SFTA2	ENST00000634371.2	TSL:5	n.288C>T		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39266 AN: 152100 Hom.: 6227 Cov.: 33

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.255

GnomAD2 exomes AF: 0.294 AC: 73813 AN: 250770 AF XY: 0.301

Gnomad AFR exome AF: 0.0755

Gnomad AMR exome AF: 0.204

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.184

Gnomad FIN exome AF: 0.391

Gnomad NFE exome AF: 0.362

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.327 AC: 477577 AN: 1461562 Hom.: 81344 Cov.: 56 AF XY: 0.326 AC XY: 236796 AN XY: 727084

African (AFR) AF: 0.0713 AC: 2388 AN: 33474

American (AMR) AF: 0.206 AC: 9204 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 9515 AN: 26132

East Asian (EAS) AF: 0.188 AC: 7457 AN: 39698

South Asian (SAS) AF: 0.229 AC: 19732 AN: 86226

European-Finnish (FIN) AF: 0.384 AC: 20452 AN: 53268

Middle Eastern (MID) AF: 0.309 AC: 1774 AN: 5732

European-Non Finnish (NFE) AF: 0.350 AC: 389206 AN: 1111944

Other (OTH) AF: 0.296 AC: 17849 AN: 60382

GnomAD4 genome AF: 0.258 AC: 39266 AN: 152216 Hom.: 6222 Cov.: 33 AF XY: 0.258 AC XY: 19176 AN XY: 74408

African (AFR) AF: 0.0816 AC: 3390 AN: 41562

American (AMR) AF: 0.226 AC: 3462 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1372 AN: 3472

East Asian (EAS) AF: 0.180 AC: 932 AN: 5174

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4830

European-Finnish (FIN) AF: 0.391 AC: 4137 AN: 10592

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24042 AN: 67968

Other (OTH) AF: 0.252 AC: 533 AN: 2112

Alfa AF: 0.320 Hom.: 27571

Bravo AF: 0.239

TwinsUK AF: 0.348 AC: 1290

ALSPAC AF: 0.357 AC: 1375

ESP6500AA AF: 0.0976 AC: 430

ESP6500EA AF: 0.362 AC: 3114

ExAC AF: 0.297 AC: 36121

Asia WGS AF: 0.152 AC: 534 AN: 3478

EpiCase AF: 0.359

EpiControl AF: 0.361

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.18
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.058
Sift4G	Pathogenic	0.0	D
Polyphen		0.35	B
Vest4		0.056
MPC		0.57
ClinPred		0.027	T
GERP RS		-1.6
Varity_R		0.044
gMVP		0.18
Mutation Taster		=98/2	polymorphism (auto)

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; COSMIC: COSV58515660;