4-68059400-C-G

Position:

• chr4-68059400-C-G

Variant summary

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

The NM_207407.2(TMPRSS11F):​c.1084G>C​(p.Asp362His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMPRSS11F NM_207407.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

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:):

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=0.30635175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS11F	NM_207407.2	c.1084G>C	p.Asp362His	missense_variant	9/10	ENST00000356291.3	NP_997290.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS11F	ENST00000356291.3	c.1084G>C	p.Asp362His	missense_variant	9/10	2	NM_207407.2	ENSP00000348639.2
UBA6-DT	ENST00000500538.7	n.1988-3207C>G		intron_variant		1
UBA6-DT	ENST00000663060.1	n.1554-20721C>G		intron_variant
UBA6-DT	ENST00000667140.1	n.1811-17879C>G		intron_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251190 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135752

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

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

Oct 10, 2023

The c.1084G>C (p.D362H) alteration is located in exon 9 (coding exon 9) of the TMPRSS11F gene. This alteration results from a G to C substitution at nucleotide position 1084, causing the aspartic acid (D) at amino acid position 362 to be replaced by a histidine (H). 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	0.35
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	0.43	N
MutationTaster	Benign	0.70	D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.43
Sift	Benign	0.16	T
Sift4G	Benign	0.38	T
Polyphen		1.0	D
Vest4		0.38
MVP		0.88
MPC		0.41
ClinPred		0.83	D
GERP RS		5.0
Varity_R		0.13
gMVP		0.70

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: rs267600210; hg19: chr4-68925118;