7-4916049-GTC-ATA

Variant names:

• chr7-4916049-GTC-ATA
• NM_198403.4:c.319_321delGACinsTAT
• MMD2 p.Asp107Tyr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_198403.4(MMD2):​c.319_321delGACinsTAT​(p.Asp107Tyr) variant causes a missense change involving the alteration of a 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. D107N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MMD2 NM_198403.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

MMD2 (HGNC:30133): (monocyte to macrophage differentiation associated 2) This gene encodes a member of the PAQR (progestin and adipoQ receptor) family. Members of this family are evolutionarily conserved with significant sequence identity to bacterial hemolysin-like proteins and are defined by a set of seven transmembrane domains. The protein encoded by this gene localizes to the Golgi apparatus to modulate Ras signaling. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198403.4. 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
	MMD2	NM_198403.4	MANE Select	c.319_321delGACinsTAT	p.Asp107Tyr	missense	N/A	NP_940685.3
	MMD2	NM_001100600.2		c.319_321delGACinsTAT	p.Asp107Tyr	missense	N/A	NP_001094070.1	Q8IY49-1
	MMD2	NM_001270375.2		c.319_321delGACinsTAT	p.Asp107Tyr	missense	N/A	NP_001257304.1	Q8IY49-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMD2	ENST00000401401.8	TSL:1 MANE Select	c.319_321delGACinsTAT	p.Asp107Tyr	missense	N/A	ENSP00000384141.3	Q8IY49-2
	MMD2	ENST00000404774.7	TSL:1	c.319_321delGACinsTAT	p.Asp107Tyr	missense	N/A	ENSP00000384690.3	Q8IY49-1
	MMD2	ENST00000406755.5	TSL:1	c.319_321delGACinsTAT	p.Asp107Tyr	missense	N/A	ENSP00000385963.1	Q8IY49-3

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		7.6

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: chr7-4955680;