5-32234970-T-C

Variant names:

• chr5-32234970-T-C
• rs1342498304
• NM_001040446.3:c.1504A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001040446.3(MTMR12):​c.1504A>G​(p.Thr502Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MTMR12 NM_001040446.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.336
• 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]

RNU6-1079P (HGNC:48042): (RNA, U6 small nuclear 1079, pseudogene)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051936924).

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.1504A>G	p.Thr502Ala	missense	Exon 14 of 16	NP_001035536.1	Q9C0I1-1
	MTMR12	NM_001294343.2		c.1504A>G	p.Thr502Ala	missense	Exon 14 of 15	NP_001281272.1	Q9C0I1-2
	MTMR12	NM_001294344.2		c.1344+4031A>G		intron	N/A	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.1504A>G	p.Thr502Ala	missense	Exon 14 of 16	ENSP00000371577.3	Q9C0I1-1
	MTMR12	ENST00000280285.9	TSL:1	c.1504A>G	p.Thr502Ala	missense	Exon 14 of 15	ENSP00000280285.5	Q9C0I1-2
	MTMR12	ENST00000851378.1		c.1648A>G	p.Thr550Ala	missense	Exon 15 of 17	ENSP00000521437.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460460 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726578

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110950

Other (OTH) AF: 0.0000166 AC: 1 AN: 60326

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.87
DANN	Benign	0.76
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.34
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.21
Sift	Benign	0.76	T
Sift4G	Benign	0.54	T
Polyphen		0.0010	B
Vest4		0.19
MVP		0.50
MPC		0.46
ClinPred		0.017	T
GERP RS		-6.2
Varity_R		0.035
gMVP		0.16
Mutation Taster		=75/25	polymorphism

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: rs1342498304; hg19: chr5-32235076; COSMIC: COSV53785212; COSMIC: COSV53785212;