4-68069985-C-A

Position:

• chr4-68069985-C-A

Variant summary

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

The NM_207407.2(TMPRSS11F):​c.537G>T​(p.Arg179Ser) 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. 13/23 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: TMPRSS11F NM_207407.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.57

Genes affected

TMPRSS11F (HGNC:29994): (transmembrane serine protease 11F) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within regulation of water loss via skin. Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

UBA6-DT (HGNC:49083): (UBA6 divergent transcript)

LOC550113 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS11F	NM_207407.2	c.537G>T	p.Arg179Ser	missense_variant	6/10	ENST00000356291.3	NP_997290.2
LOC550113	NR_046116.1	n.2659-3120C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS11F	ENST00000356291.3	c.537G>T	p.Arg179Ser	missense_variant	6/10	2	NM_207407.2	ENSP00000348639	P1
UBA6-DT	ENST00000500538.7	n.2602+6764C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Mar 06, 2023

The c.537G>T (p.R179S) alteration is located in exon 6 (coding exon 6) of the TMPRSS11F gene. This alteration results from a G to T substitution at nucleotide position 537, causing the arginine (R) at amino acid position 179 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.0077	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.95	N
REVEL	Uncertain	0.46
Sift	Benign	0.070	T
Sift4G	Benign	0.064	T
Polyphen		0.30	B
Vest4		0.41
MutPred		0.30		Loss of MoRF binding (P = 0.0274);
MVP		0.27
MPC		0.42
ClinPred		0.92	D
GERP RS		-8.0
Varity_R		0.21
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.33		Position offset: -16

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: chr4-68935703;