rs12331141

Positions:

• chr4-68229479-T-A
• chr4-68229479-T-C
• chr4-68229479-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000332644.6(TMPRSS11B):​c.724A>T​(p.Ile242Phe) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I242V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMPRSS11B ENST00000332644.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18384522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS11B	NM_182502.3	c.724A>T	p.Ile242Phe	missense_variant	8/10	ENST00000332644.6	NP_872308.2
TMPRSS11B	XM_011531608.3	c.724A>T	p.Ile242Phe	missense_variant	8/11		XP_011529910.1
TMPRSS11B	XM_011531609.1	c.687-127A>T		intron_variant			XP_011529911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS11B	ENST00000332644.6	c.724A>T	p.Ile242Phe	missense_variant	8/10	1	NM_182502.3	ENSP00000330475	P1
TMPRSS11B	ENST00000510856.1	n.200A>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Benign	0.68
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.76
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.16
Sift	Benign	0.75	T
Sift4G	Benign	0.56	T
Polyphen		0.13	B
Vest4		0.16
MutPred		0.68		Gain of catalytic residue at I242 (P = 0.0047);
MVP		0.28
MPC		0.046
ClinPred		0.11	T
GERP RS		0.64
Varity_R		0.11
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12331141; hg19: chr4-69095197;