4-68232414-T-C

Variant names:

• chr4-68232414-T-C
• NM_182502.3:c.472A>G

Variant summary

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

The NM_182502.3(TMPRSS11B):​c.472A>G​(p.Ile158Val) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS11B	NM_182502.3	MANE Select	c.472A>G	p.Ile158Val	missense splice_region	Exon 6 of 10	NP_872308.2	Q86T26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS11B	ENST00000332644.6	TSL:1 MANE Select	c.472A>G	p.Ile158Val	missense splice_region	Exon 6 of 10	ENSP00000330475.5	Q86T26
	TMPRSS11B	ENST00000502365.1	TSL:1	n.605A>G		splice_region non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.047
Sift	Benign	0.15	T
Sift4G	Benign	0.30	T
Polyphen		0.051	B
Vest4		0.19
MutPred		0.29		Gain of ubiquitination at K154 (P = 0.1317)
MVP		0.076
MPC		0.040
ClinPred		0.45	T
GERP RS		4.5
Varity_R		0.066
gMVP		0.25
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr4-69098132;