6-30951924-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

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]

HCG21 (HGNC:31335): (HLA complex group 21)

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUCL3	NM_080870.4	c.3460T>C	p.Leu1154Leu	synonymous_variant	Exon 2 of 3	ENST00000462446.6	NP_543146.2
HCG21	NR_138040.1	n.256+438A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUCL3	ENST00000462446.6	c.3460T>C	p.Leu1154Leu	synonymous_variant	Exon 2 of 3	5	NM_080870.4	ENSP00000417182.1
MUCL3	ENST00000636043.1	c.3661T>C	p.Leu1221Leu	synonymous_variant	Exon 5 of 6	5		ENSP00000490368.1
SFTA2	ENST00000634371.1	c.-9+438A>G		intron_variant	Intron 4 of 5	5		ENSP00000489572.1
HCG21	ENST00000419481.1	n.224+1143A>G		intron_variant	Intron 2 of 2	3

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

GnomAD3 exomes AF: 0.324 AC: 81094 AN: 250296 Hom.: 13944 AF XY: 0.332 AC XY: 44971 AN XY: 135310

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 SAS 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

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.374

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.362

Gnomad4 OTH exome AF: 0.320

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

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.284

Alfa AF: 0.352 Hom.: 16275

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.66
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs2517449; hg19: chr6-30919701; COSMIC: COSV58517855;