chr6-30951924-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_080870.4(MUCL3):​c.3460T>C​(p.Leu1154Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,612,734 control chromosomes in the GnomAD database, including 96,345 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6987 hom., cov: 31)
  • Exomes 𝑓: 0.35 (89358 hom.)
• Consequence: MUCL3 NM_080870.4 synonymous
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-5.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 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.3460T>C	p.Leu1154Leu	synonymous	Exon 2 of 3	NP_543146.2
	HCG21	NR_138040.1		n.256+438A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUCL3	ENST00000462446.6	TSL:5 MANE Select	c.3460T>C	p.Leu1154Leu	synonymous	Exon 2 of 3	ENSP00000417182.1
	HCG21	ENST00000419481.1	TSL:3	n.224+1143A>G		intron	N/A
	SFTA2	ENST00000634371.2	TSL:5	n.513+438A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43172 AN: 151238 Hom.: 6988 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.285

GnomAD2 exomes AF: 0.324 AC: 81094 AN: 250296 AF XY: 0.332

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.381

Gnomad EAS exome AF: 0.304

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.374

Gnomad OTH exome AF: 0.342

GnomAD4 exome AF: 0.345 AC: 504354 AN: 1461378 Hom.: 89358 Cov.: 97 AF XY: 0.346 AC XY: 251193 AN XY: 727034

African (AFR) AF: 0.119 AC: 3967 AN: 33402

American (AMR) AF: 0.221 AC: 9873 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 9763 AN: 26128

East Asian (EAS) AF: 0.258 AC: 10227 AN: 39694

South Asian (SAS) AF: 0.302 AC: 26065 AN: 86204

European-Finnish (FIN) AF: 0.388 AC: 20703 AN: 53362

Middle Eastern (MID) AF: 0.332 AC: 1913 AN: 5768

European-Non Finnish (NFE) AF: 0.362 AC: 402528 AN: 1111864

Other (OTH) AF: 0.320 AC: 19315 AN: 60378

GnomAD4 genome AF: 0.285 AC: 43191 AN: 151356 Hom.: 6987 Cov.: 31 AF XY: 0.286 AC XY: 21184 AN XY: 73960

African (AFR) AF: 0.128 AC: 5275 AN: 41188

American (AMR) AF: 0.246 AC: 3742 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1394 AN: 3464

East Asian (EAS) AF: 0.275 AC: 1416 AN: 5148

South Asian (SAS) AF: 0.297 AC: 1419 AN: 4778

European-Finnish (FIN) AF: 0.396 AC: 4139 AN: 10456

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24818 AN: 67794

Other (OTH) AF: 0.284 AC: 596 AN: 2098

Alfa AF: 0.341 Hom.: 35006

Bravo AF: 0.267

Asia WGS AF: 0.251 AC: 877 AN: 3478

EpiCase AF: 0.372

EpiControl AF: 0.375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.66
DANN	Benign	0.82
PhyloP100		-5.7
Mutation Taster		=100/0	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: rs2517449; hg19: chr6-30919701; COSMIC: COSV58517855;