NM_001040446.3:c.1995G>A

Variant names:

• chr5-32230027-C-T
• rs1747931585
• NM_001040446.3:c.1995G>A

Variant summary

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

The NM_001040446.3(MTMR12):​c.1995G>A​(p.Leu665Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,370 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: 6.8e-7 (0 hom.)
• Consequence: MTMR12 NM_001040446.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.706
• Publications: 0 publications found

Genes affected

MTMR12 (HGNC:18191): (myotubularin related protein 12) Phosphatidylinositide 3-kinase-derived membrane-anchored phosphatidylinositides, such as phosphatidylinositol 3-phosphate (PtdIns(3)P), regulate diverse cellular processes. The protein encoded by this gene functions as an adaptor subunit in a complex with an active PtdIns(3)P 3-phosphatase. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

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=0.706 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040446.3. 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
	MTMR12	NM_001040446.3	MANE Select	c.1995G>A	p.Leu665Leu	synonymous	Exon 16 of 16	NP_001035536.1	Q9C0I1-1
	MTMR12	NM_001294343.2		c.1833G>A	p.Leu611Leu	synonymous	Exon 15 of 15	NP_001281272.1	Q9C0I1-2
	MTMR12	NM_001294344.2		c.1665G>A	p.Leu555Leu	synonymous	Exon 14 of 14	NP_001281273.1	Q9C0I1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR12	ENST00000382142.8	TSL:1 MANE Select	c.1995G>A	p.Leu665Leu	synonymous	Exon 16 of 16	ENSP00000371577.3	Q9C0I1-1
	MTMR12	ENST00000280285.9	TSL:1	c.1833G>A	p.Leu611Leu	synonymous	Exon 15 of 15	ENSP00000280285.5	Q9C0I1-2
	MTMR12	ENST00000851378.1		c.2139G>A	p.Leu713Leu	synonymous	Exon 17 of 17	ENSP00000521437.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461370 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726876

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111574

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.7
DANN	Benign	0.82
PhyloP100		0.71

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: rs1747931585; hg19: chr5-32230133;