4-68229479-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 16/21 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 NM_182502.3 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=0.081541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS11B	NM_182502.3	c.724A>C	p.Ile242Leu	missense_variant	Exon 8 of 10	ENST00000332644.6	NP_872308.2
TMPRSS11B	XM_011531608.3	c.724A>C	p.Ile242Leu	missense_variant	Exon 8 of 11		XP_011529910.1
TMPRSS11B	XM_011531609.1	c.687-127A>C		intron_variant	Intron 7 of 7		XP_011529911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS11B	ENST00000332644.6	c.724A>C	p.Ile242Leu	missense_variant	Exon 8 of 10	1	NM_182502.3	ENSP00000330475.5
TMPRSS11B	ENST00000510856.1	n.200A>C		non_coding_transcript_exon_variant	Exon 1 of 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	0.071
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
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

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: rs12331141; hg19: chr4-69095197;