4-68474745-C-T

Variant names:

• chr4-68474745-C-T
• rs925013905
• NM_014058.4:c.513C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_014058.4(TMPRSS11E):​c.513C>T​(p.Asp171Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000896 in 1,451,654 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: TMPRSS11E NM_014058.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=0.305 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014058.4. 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
	TMPRSS11E	NM_014058.4	MANE Select	c.513C>T	p.Asp171Asp	synonymous	Exon 6 of 10	NP_054777.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS11E	ENST00000305363.9	TSL:1 MANE Select	c.513C>T	p.Asp171Asp	synonymous	Exon 6 of 10	ENSP00000307519.4	Q9UL52
	TMPRSS11E	ENST00000510647.1	TSL:3	n.337C>T		non_coding_transcript_exon	Exon 4 of 6	ENSP00000424109.1	H0Y9G7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000419 AC: 1 AN: 238498 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000922

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000896 AC: 13 AN: 1451654 Hom.: 0 Cov.: 30 AF XY: 0.0000125 AC XY: 9 AN XY: 721804

African (AFR) AF: 0.00 AC: 0 AN: 32870

American (AMR) AF: 0.00 AC: 0 AN: 42442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39358

South Asian (SAS) AF: 0.00 AC: 0 AN: 83258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00000902 AC: 10 AN: 1108604

Other (OTH) AF: 0.0000333 AC: 2 AN: 60066

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000254 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	10
DANN	Uncertain	0.98
PhyloP100		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs925013905; hg19: chr4-69340463;