chr4-68478863-C-G

Position:

• chr4-68478863-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014058.4(TMPRSS11E):​c.982C>G​(p.His328Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMPRSS11E NM_014058.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.467

Genes affected

TMPRSS11E (HGNC:24465): (transmembrane serine protease 11E) Predicted to enable serine-type peptidase activity. Involved in cognition. Predicted to be integral component of plasma membrane. Predicted to be active 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=0.16692534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMPRSS11E	NM_014058.4	c.982C>G	p.His328Asp	missense_variant	9/10	ENST00000305363.9
TMPRSS11E	XM_011531896.3	c.748C>G	p.His250Asp	missense_variant	8/9
TMPRSS11E	XM_047450139.1	c.748C>G	p.His250Asp	missense_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS11E	ENST00000305363.9	c.982C>G	p.His328Asp	missense_variant	9/10	1	NM_014058.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461416 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727012

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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 20, 2021

The c.982C>G (p.H328D) alteration is located in exon 9 (coding exon 9) of the TMPRSS11E gene. This alteration results from a C to G substitution at nucleotide position 982, causing the histidine (H) at amino acid position 328 to be replaced by an aspartic acid (D). 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	0.14
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Benign	0.64
DEOGEN2	Benign	0.052	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.060	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.27
Sift	Benign	0.62	T
Sift4G	Benign	0.63	T
Polyphen		0.14	B
Vest4		0.46
MutPred		0.45		Gain of phosphorylation at Y324 (P = 0.1242);
MVP		0.53
MPC		0.20
ClinPred		0.038	T
GERP RS		-1.0
Varity_R		0.25
gMVP		0.80

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: chr4-69344581;