rs144601347

Variant names:

• chr11-118103213-G-A
• rs144601347
• NM_019894.4:c.270G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-118103213-G-A
• chr11-118103213-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_019894.4(TMPRSS4):​c.270G>A​(p.Glu90Glu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMPRSS4 NM_019894.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.011).
• BP7: Synonymous conserved (PhyloP=0.116 with no splicing effect.

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.270G>A	p.Glu90Glu	synonymous	Exon 4 of 13	NP_063947.2	Q9NRS4-1
	TMPRSS4	NM_001173551.2		c.264G>A	p.Glu88Glu	synonymous	Exon 4 of 13	NP_001167022.2	Q9NRS4-3
	TMPRSS4	NM_001083947.2		c.270G>A	p.Glu90Glu	synonymous	Exon 4 of 13	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.270G>A	p.Glu90Glu	synonymous	Exon 4 of 13	ENSP00000416037.3	Q9NRS4-1
	TMPRSS4	ENST00000522824.5	TSL:1	c.270G>A	p.Glu90Glu	synonymous	Exon 4 of 13	ENSP00000430547.1	Q9NRS4-2
	TMPRSS4	ENST00000714375.1		n.270G>A		non_coding_transcript_exon	Exon 4 of 12	ENSP00000519642.1	A0AAQ5BHV3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.62
PhyloP100		0.12

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

Other links and lift over

dbSNP: rs144601347; hg19: chr11-117973928;