6-30948940-C-T

Variant names:

• chr6-30948940-C-T
• rs367634528
• NM_080870.4:c.476C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_080870.4(MUCL3):​c.476C>T​(p.Thr159Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 1,551,006 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (1 hom.)
• Consequence: MUCL3 NM_080870.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.539
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023786604).

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.476C>T	p.Thr159Met	missense	Exon 2 of 3	NP_543146.2	E9PEI6
	HCG21	NR_138040.1		n.257-2362G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUCL3	ENST00000462446.6	TSL:5 MANE Select	c.476C>T	p.Thr159Met	missense	Exon 2 of 3	ENSP00000417182.1	E9PEI6
	HCG21	ENST00000419481.1	TSL:3	n.225-2581G>A		intron	N/A
	SFTA2	ENST00000634371.2	TSL:5	n.513+3422G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000653 AC: 100 AN: 153240 AF XY: 0.000652

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000734

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000916

Gnomad FIN exome AF: 0.000327

Gnomad NFE exome AF: 0.000928

Gnomad OTH exome AF: 0.000232

GnomAD4 exome AF: 0.000525 AC: 734 AN: 1398710 Hom.: 1 Cov.: 30 AF XY: 0.000526 AC XY: 363 AN XY: 689908

African (AFR) AF: 0.0000635 AC: 2 AN: 31480

American (AMR) AF: 0.000704 AC: 25 AN: 35504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35738

South Asian (SAS) AF: 0.000961 AC: 76 AN: 79086

European-Finnish (FIN) AF: 0.000223 AC: 11 AN: 49266

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5698

European-Non Finnish (NFE) AF: 0.000548 AC: 591 AN: 1078810

Other (OTH) AF: 0.000449 AC: 26 AN: 57958

GnomAD4 genome AF: 0.000374 AC: 57 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.000389 AC XY: 29 AN XY: 74476

African (AFR) AF: 0.0000962 AC: 4 AN: 41572

American (AMR) AF: 0.000589 AC: 9 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000564 Hom.: 0

Bravo AF: 0.000397

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000943 AC: 3

ExAC AF: 0.000523 AC: 12

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.54
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.10
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.30
MVP		0.20
MPC		1.4
ClinPred		0.052	T
GERP RS		2.3
Varity_R		0.029
gMVP		0.13
Mutation Taster		=94/6	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: rs367634528; hg19: chr6-30916717; COSMIC: COSV58518363;