1-149929140-C-G

Variant names:

• chr1-149929140-C-G
• rs373466760
• NM_001145862.2:c.2119G>C

Variant summary

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

The NM_001145862.2(MTMR11):​c.2119G>C​(p.Asp707His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D707Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MTMR11 NM_001145862.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 0 publications found

Genes affected

MTMR11 (HGNC:24307): (myotubularin related protein 11) Predicted to enable phosphatidylinositol-3-phosphatase activity. Predicted to be involved in phosphatidylinositol dephosphorylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.043636233).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145862.2. 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
	MTMR11	NM_001145862.2	MANE Select	c.2119G>C	p.Asp707His	missense	Exon 17 of 17	NP_001139334.1	A4FU01-1
	MTMR11	NM_181873.3		c.1888+15G>C		intron	N/A	NP_870988.2	A4FU01-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR11	ENST00000439741.4	TSL:2 MANE Select	c.2119G>C	p.Asp707His	missense	Exon 17 of 17	ENSP00000391668.2	A4FU01-1
	MTMR11	ENST00000466496.5	TSL:1	n.1439G>C		non_coding_transcript_exon	Exon 10 of 10
	MTMR11	ENST00000482343.5	TSL:1	n.2248G>C		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.097
DANN	Benign	0.62
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.6
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.20
Sift	Benign	0.28	T
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.045
MVP		0.14
MPC		0.22
ClinPred		0.053	T
GERP RS		-8.0
Varity_R		0.041
gMVP		0.34
Mutation Taster		=100/0	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: rs373466760; hg19: chr1-149901032;