4-68228800-A-C

Position:

• chr4-68228800-A-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.1031T>G​(p.Phe344Cys) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMPRSS11B NM_182502.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.446

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=0.23963761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS11B	NM_182502.3	c.1031T>G	p.Phe344Cys	missense_variant	9/10	ENST00000332644.6	NP_872308.2
TMPRSS11B	XM_011531608.3	c.1031T>G	p.Phe344Cys	missense_variant	9/11		XP_011529910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS11B	ENST00000332644.6	c.1031T>G	p.Phe344Cys	missense_variant	9/10	1	NM_182502.3	ENSP00000330475.5
TMPRSS11B	ENST00000510856.1	n.507T>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.1031T>G (p.F344C) alteration is located in exon 9 (coding exon 9) of the TMPRSS11B gene. This alteration results from a T to G substitution at nucleotide position 1031, causing the phenylalanine (F) at amino acid position 344 to be replaced by a cysteine (C). 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	0.20
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	2.0
DANN	Benign	0.67
DEOGEN2	Benign	0.24	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.19	T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.20	N
REVEL	Uncertain	0.33
Sift	Benign	0.19	T
Sift4G	Benign	0.20	T
Polyphen		0.34	B
Vest4		0.25
MutPred		0.52		Loss of glycosylation at S342 (P = 0.0144);
MVP		0.25
MPC		0.068
ClinPred		0.21	T
GERP RS		-2.4
Varity_R		0.056
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-69094518;