17-75486315-TCG-CTC

Variant names:

• chr17-75486315-TCG-CTC
• NM_014738.6:c.298_300delTCGinsCTC
• TMEM94 p.Ser100Leu

Variant summary

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

The NM_014738.6(TMEM94):​c.298_300delTCGinsCTC​(p.Ser100Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S100W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM94 NM_014738.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 0 publications found

Genes affected

TMEM94 (HGNC:28983): (transmembrane protein 94) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM94 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with cardiac defects and dysmorphic facies

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Orphanet, ClinGen, Ambry Genetics

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014738.6. 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
	TMEM94	NM_014738.6	MANE Select	c.298_300delTCGinsCTC	p.Ser100Leu	missense	N/A	NP_055553.3
	TMEM94	NM_001438842.1		c.298_300delTCGinsCTC	p.Ser100Leu	missense	N/A	NP_001425771.1
	TMEM94	NM_001438843.1		c.328_330delTCGinsCTC	p.Ser110Leu	missense	N/A	NP_001425772.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM94	ENST00000314256.12	TSL:1 MANE Select	c.298_300delTCGinsCTC	p.Ser100Leu	missense	N/A	ENSP00000313885.7	Q12767-1
	TMEM94	ENST00000956011.1		c.298_300delTCGinsCTC	p.Ser100Leu	missense	N/A	ENSP00000626070.1
	TMEM94	ENST00000861539.1		c.298_300delTCGinsCTC	p.Ser100Leu	missense	N/A	ENSP00000531598.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.0070

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: chr17-73482396;