4-68229479-T-G

Variant names:

• chr4-68229479-T-G
• rs12331141
• NM_182502.3:c.724A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182502.3(TMPRSS11B):​c.724A>C​(p.Ile242Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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: 32)
• Consequence: TMPRSS11B NM_182502.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 25 publications found

Genes affected

TMPRSS11B (HGNC:25398): (transmembrane serine protease 11B) Enables serine-type peptidase activity. Predicted to be involved in proteolysis. Located in plasma membrane. [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=0.081541).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182502.3. 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
	TMPRSS11B	NM_182502.3	MANE Select	c.724A>C	p.Ile242Leu	missense	Exon 8 of 10	NP_872308.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS11B	ENST00000332644.6	TSL:1 MANE Select	c.724A>C	p.Ile242Leu	missense	Exon 8 of 10	ENSP00000330475.5
	TMPRSS11B	ENST00000510856.1	TSL:3	n.200A>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.66
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.90
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.53	N
PhyloP100		1.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.16
Sift	Benign	0.86	T
Sift4G	Benign	0.86	T
Polyphen		0.0030	B
Vest4		0.14
MutPred		0.52		Loss of methylation at K246 (P = 0.0738)
MVP		0.15
MPC		0.028
ClinPred		0.037	T
GERP RS		0.64
Varity_R		0.095
gMVP		0.44
Mutation Taster		=97/3	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: rs12331141; hg19: chr4-69095197;