11-118113399-GCC-TCT

Variant names:

• chr11-118113399-GCC-TCT
• NM_019894.4:c.874_876delGCCinsTCT
• TMPRSS4 p.Ala292Ser

Variant summary

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

The NM_019894.4(TMPRSS4):​c.874_876delGCCinsTCT​(p.Ala292Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A292T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TMPRSS4 NM_019894.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.45
• Publications: 0 publications found

Genes affected

TMPRSS4 (HGNC:11878): (transmembrane serine protease 4) This gene encodes a member of the serine protease family. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified as a gene overexpressed in pancreatic carcinoma. The encoded protein is membrane bound with a N-terminal anchor sequence and a glycosylated extracellular region containing the serine protease domain. The protein has been found to promote SARS-CoV-2 entry into host cells. [provided by RefSeq, Aug 2021]

TMPRSS4 Gene-Disease associations (from GenCC):

• autosomal recessive cerebral atrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019894.4. 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
	TMPRSS4	NM_019894.4	MANE Select	c.874_876delGCCinsTCT	p.Ala292Ser	missense	N/A	NP_063947.2	Q9NRS4-1
	TMPRSS4	NM_001173551.2		c.868_870delGCCinsTCT	p.Ala290Ser	missense	N/A	NP_001167022.2	Q9NRS4-3
	TMPRSS4	NM_001083947.2		c.859_861delGCCinsTCT	p.Ala287Ser	missense	N/A	NP_001077416.2	Q9NRS4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS4	ENST00000437212.8	TSL:1 MANE Select	c.874_876delGCCinsTCT	p.Ala292Ser	missense	N/A	ENSP00000416037.3	Q9NRS4-1
	TMPRSS4	ENST00000522824.5	TSL:1	c.859_861delGCCinsTCT	p.Ala287Ser	missense	N/A	ENSP00000430547.1	Q9NRS4-2
	TMPRSS4	ENST00000714375.1		n.874_876delGCCinsTCT		non_coding_transcript_exon	Exon 9 of 12	ENSP00000519642.1	A0AAQ5BHV3

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-117984114;