rs2302190

Variant names:

• chr17-58507147-T-A
• rs2302190
• NM_001378067.1:c.880A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-58507147-T-A
• chr17-58507147-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001378067.1(MTMR4):​c.880A>T​(p.Ser294Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,950 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: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: MTMR4 NM_001378067.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 40 publications found

Genes affected

MTMR4 (HGNC:7452): (myotubularin related protein 4) Enables protein phosphatase binding activity. Involved in regulation of phosphatidylinositol dephosphorylation. Located in endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35492015).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378067.1. 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
	MTMR4	NM_001378067.1	MANE Select	c.880A>T	p.Ser294Cys	missense	Exon 8 of 18	NP_001364996.1	A0A804HJV7
	MTMR4	NM_001378066.1		c.850A>T	p.Ser284Cys	missense	Exon 10 of 20	NP_001364995.1
	MTMR4	NM_004687.5		c.838A>T	p.Ser280Cys	missense	Exon 9 of 19	NP_004678.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR4	ENST00000682306.1	MANE Select	c.880A>T	p.Ser294Cys	missense	Exon 8 of 18	ENSP00000507664.1	A0A804HJV7
	MTMR4	ENST00000323456.9	TSL:1	c.838A>T	p.Ser280Cys	missense	Exon 9 of 19	ENSP00000325285.5	Q9NYA4
	MTMR4	ENST00000955804.1		c.976A>T	p.Ser326Cys	missense	Exon 9 of 19	ENSP00000625863.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151950 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151950 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74206

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41328

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 14271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.75	D
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.35	T
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.1
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.025	D
Polyphen		0.89	P
Vest4		0.34
MutPred		0.42		Loss of relative solvent accessibility (P = 0.0404)
MVP		0.49
MPC		1.3
ClinPred		0.97	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.15
gMVP		0.61

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: rs2302190; hg19: chr17-56584508;