4-68234484-G-A

Variant names:

• chr4-68234484-G-A
• NM_182502.3:c.448C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182502.3(TMPRSS11B):​c.448C>T​(p.Pro150Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMPRSS11B NM_182502.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2804597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS11B	NM_182502.3	c.448C>T	p.Pro150Ser	missense_variant	Exon 5 of 10	ENST00000332644.6	NP_872308.2
TMPRSS11B	XM_011531608.3	c.448C>T	p.Pro150Ser	missense_variant	Exon 5 of 11		XP_011529910.1
TMPRSS11B	XM_011531609.1	c.448C>T	p.Pro150Ser	missense_variant	Exon 5 of 8		XP_011529911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS11B	ENST00000332644.6	c.448C>T	p.Pro150Ser	missense_variant	Exon 5 of 10	1	NM_182502.3	ENSP00000330475.5
TMPRSS11B	ENST00000502365.1	n.581C>T		non_coding_transcript_exon_variant	Exon 5 of 6	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.448C>T (p.P150S) alteration is located in exon 5 (coding exon 5) of the TMPRSS11B gene. This alteration results from a C to T substitution at nucleotide position 448, causing the proline (P) at amino acid position 150 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.064	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.064
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.23
Sift	Benign	0.38	T
Sift4G	Benign	0.68	T
Polyphen		1.0	D
Vest4		0.25
MutPred		0.62		Gain of MoRF binding (P = 0.036);
MVP		0.30
MPC		0.061
ClinPred		0.85	D
GERP RS		5.2
Varity_R		0.11
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-69100202;